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Ubiquitin ligase subunit FBXO9 inhibits V-ATPase assembly and impedes lung cancer metastasis Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-14 Liang Liu, Xiaodong Chen, Leilei Wu, Kaizong Huang, Zhenyi Wang, Yaolin Zheng, Cheng Zheng, Zhenshan Zhang, Jiayan Chen, Jiaming Wei, Song Chen, Weilin Jin, Jinfei Chen, Dongping Wei, Yaping Xu
The evolutionarily conserved protein FBXO9 acts as a substrate receptor for the SKP1-cullin-1-RBX1 ubiquitin ligase and is implicated in cancer, exhibiting either tumor-suppressive or oncogenic effects depending on the specific tumor type. However, their role in lung cancer metastasis remains unclear. Lentiviral vectors carrying miRNA-based shRNA sequences for gene-specific knockdown were generated
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Harnessing ferroptosis for enhanced sarcoma treatment: mechanisms, progress and prospects Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-12 Jing Zeng, Xianghong Zhang, Zhengjun Lin, Yu Zhang, Jing Yang, Pengcheng Dou, Tang Liu
Sarcoma is a malignant tumor that originates from mesenchymal tissue. The common treatment for sarcoma is surgery supplemented with radiotherapy and chemotherapy. However, patients have a 5-year survival rate of only approximately 60%, and sarcoma cells are highly resistant to chemotherapy. Ferroptosis is an iron-dependent nonapoptotic type of regulated programmed cell death that is closely related
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Suppression of A-to-I RNA-editing enzyme ADAR1 sensitizes hepatocellular carcinoma cells to oxidative stress through regulating Keap1/Nrf2 pathway Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-11 Houhong Wang, Xiaoyu Wei, Lu Liu, Junfeng Zhang, Heng Li
A-to-I RNA editing is an abundant post-transcriptional modification event in hepatocellular carcinoma (HCC). Evidence suggests that adenosine deaminases acting on RNA 1 (ADAR1) correlates to oxidative stress that is a crucial factor of HCC pathogenesis. The present study investigated the effect of ADAR1 on survival and oxidative stress of HCC, and underlying mechanisms. ADAR1 expression was measured
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MSCsDB: a database of single-cell transcriptomic profiles and in-depth comprehensive analyses of human mesenchymal stem cells Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-06 Miao Yu, Ke Sui, Zheng Wang, Xi Zhang
Mesenchymal stem cells (MSCs) possess multipotent properties that make them promising candidates for immunomodulation and regenerative medicine. However, MSC heterogeneity poses challenges to their research reproducibility and clinical application. The emergence of single-cell RNA sequencing (scRNA-seq) technology has enabled a thorough examination of MSC heterogeneity, underscoring the necessity for
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Cytokine-based models for efficient differentiation between infection and cytokine release syndrome in patients with hematological malignancies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-05 Linqin Wang, Yuqi Lv, Linghui Zhou, Shenghao Wu, Yuanyuan Zhu, Shan Fu, Shuyi Ding, Ruimin Hong, Mingming Zhang, Hanjing Yu, Alex H. Chang, Guoqing Wei, Yongxian Hu, He Huang
Although the efficacy of chimeric antigen receptor (CAR)-T cell therapy has been widely demonstrated, its clinical application is hampered by the complexity and fatality of its side effects. Cytokine release syndrome (CRS) is the most common toxicity following CAR-T cell infusion, and its symptoms substantially overlap with those of infection. Whereas, current diagnostic techniques for infections are
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The multi-CDK inhibitor dinaciclib reverses bromo- and extra-terminal domain (BET) inhibitor resistance in acute myeloid leukemia via inhibition of Wnt/β-catenin signaling Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-04 Alexander R. Marr, Madeline Halpin, Dominique L. Corbin, Yerdanos Asemelash, Steven Sher, Britten K. Gordon, Ethan C. Whipp, Shaneice Mitchell, Bonnie K. Harrington, Shelley Orwick, Samon Benrashid, Virginia M. Goettl, Vedat Yildiz, Andrew D. Mitchell, Olivia Cahn, Alice S. Mims, Karilyn T. M. Larkin, Meixao Long, James Blachly, Jennifer A. Woyach, Rosa Lapalombella, Nicole R. Grieselhuber
Acute myeloid leukemia (AML) is a highly aggressive hematologic cancer with poor survival across a broad range of molecular subtypes. Development of efficacious and well-tolerable therapies encompassing the range of mutations that can arise in AML remains an unmet need. The bromo- and extra-terminal domain (BET) family of proteins represents an attractive therapeutic target in AML due to their crucial
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Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-01 Ling Zhou, Yunlong Lu, Wei Liu, Shanglong Wang, Lingling Wang, Pengdou Zheng, Guisha Zi, Huiguo Liu, Wukun Liu, Shuang Wei
A drug conjugate consists of a cytotoxic drug bound via a linker to a targeted ligand, allowing the targeted delivery of the drug to one or more tumor sites. This approach simultaneously reduces drug toxicity and increases efficacy, with a powerful combination of efficient killing and precise targeting. Antibody‒drug conjugates (ADCs) are the best-known type of drug conjugate, combining the specificity
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Dual-targeted CAR T-cell immunotherapies for hematological malignancies: latest updates from the 2023 ASH annual meeting Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-27 Jingyi Yang, Hao Guo, Lu Han, Yongping Song, Keshu Zhou
Over the past few years, dual-targeted chimeric antigen receptor (CAR) T-cell therapy has been employed in the management of hematological malignancies to mitigate treatment failure, particularly in cases of antigen escape. The most widely used approaches include CD19/CD20, CD20/CD22, and BCMA/CD19 CAR T-cells. Alternative immune cells, including natural killer T cells and invariant natural killer
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The abundance of the short GATA1 isoform affects megakaryocyte differentiation and leukemic predisposition in mice Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-26 Daishi Ishihara, Atsushi Hasegawa, Ikuo Hirano, James Douglas Engel, Masayuki Yamamoto, Ritsuko Shimizu
Transcription factor GATA1 controls the delicate balance between proliferation, differentiation and apoptosis in both the erythroid and megakaryocytic lineages. In addition to full-length GATA1, there is an GATA1 isoform, GATA1s, that lacks the amino-terminal transactivation domain. Somatic GATA1 mutations that lead to the exclusive production of GATA1s appear to be necessary and sufficient for the
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Strain-dependent modifiers exacerbate familial leukemia caused by GATA1-deficiency Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-26 Ikuo Hirano, Kanako Abe, James Douglas Engel, Masayuki Yamamoto, Ritsuko Shimizu
GATA1 plays a critical role in differentiation, proliferation, and apoptosis during erythropoiesis. We developed a Gata1 knock-down allele (Gata1.05) that results in GATA1 expression at 5% of endogenous level. In female mice heterozygous for both the Gata1.05 and wild-type alleles, we observed a predisposition to erythroblastic leukemia three to six months after birth. Since no male Gata1.05 progeny
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Challenges and strategies associated with CAR-T cell therapy in blood malignancies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-24 Zhaoyun Liu, Wenhui Lei, Hao Wang, Xiaohan Liu, Rong Fu
Cellular immunotherapy, particularly CAR-T cells, has shown potential in the improvement of outcomes in patients with refractory and recurrent malignancies of the blood. However, achieving sustainable long-term complete remission for blood cancer remains a challenge, with resistance and relapse being expected outcomes for many patients. Although many studies have attempted to clarify the mechanisms
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Targeting natural killer cells: from basic biology to clinical application in hematologic malignancies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-23 Juanjuan Shang, Shunfeng Hu, Xin Wang
Natural killer (NK) cell belongs to innate lymphoid cell family that contributes to host immunosurveillance and defense without pre-immunization. Emerging studies have sought to understand the underlying mechanism behind NK cell dysfunction in tumor environments, and provide numerous novel therapeutic targets for tumor treatment. Strategies to enhance functional activities of NK cell have exhibited
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Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-22 Xiao-Tian Shen, Sun-Zhe Xie, Xin Zheng, Tian-Tian Zou, Bei-Yuan Hu, Jing Xu, Lu Liu, Yun-Feng Xu, Xu-Feng Wang, Hao Wang, Shun Wang, Le Zhu, Kang-Kang Yu, Wen-Wei Zhu, Lu Lu, Ju-Bo Zhang, Jin-Hong Chen, Qiong-Zhu Dong, Lu-Yu Yang, Lun-Xiu Qin
Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied
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Low-dose hypomethylating agents cooperate with ferroptosis inducers to enhance ferroptosis by regulating the DNA methylation-mediated MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway in acute myeloid leukemia Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-20 Shuya Feng, Yigang Yuan, Zihan Lin, Min Li, Daijiao Ye, Liuzhi Shi, Danyang Li, Min Zhao, Chen Meng, Xiaofei He, Shanshan Wu, Fang Xiong, Siyu Ye, Junjun Yang, Haifeng Zhuang, Lili Hong, Shenmeng Gao
Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML.
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Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-19 Tian-Qi Chen, Heng-Jing Huang, Shun-Xin Zhu, Xiao-Tong Chen, Ke-Jia Pu, Dan Wang, Yan An, Jun-Yi Lian, Yu-Meng Sun, Yue-Qin Chen, Wen-Tao Wang
Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with
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Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2023 ASH annual meeting Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-16 Xubo Gong, Xin He, Lin Wang, Teng Yu, Weiwei Liu, Huiying Xu, Lan Jin, Xiang Li, Bin Zhang, Zhihua Tao, Wenbin Qian
Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) often exhibit limited responses to traditional chemotherapy, resulting in poor prognosis. The combination of venetoclax (VEN) with hypomethylating agents has been established as the standard treatment for elderly or medically unfit AML patients unable to undergo intensive chemotherapy. Despite this, the availability of novel VEN-based
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Outcomes of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: validation, comparison and improvement of 2022 ELN genetic risk system Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-15 Haixiao Zhang, Xinhui Zheng, Wenwen Guo, Yonghui Xia, Rongli Zhang, Weihua Zhai, Xin Chen, Qiaoling Ma, Donglin Yang, Jialin Wei, Aiming Pang, Yi He, Sizhou Feng, Jianxiang Wang, Mingzhe Han, Erlie Jiang
The 2022 European LeukemiaNet (ELN) updated the previous risk classification published in 2017 but the prognostic significance for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We enrolled 600 acute myeloid leukemia (AML) patients who underwent allo-HSCT to validate ELN-2022 genetic risk system and compared it with ELN-2017. There were 214 (35.67%), 162 (27.0%), and
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Revealing the role of the gut microbiota in enhancing targeted therapy efficacy for lung adenocarcinoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-09 Ting Jiang, Meng Zhang, Shaoyu Hao, Shi Huang, Xin Zheng, Zheng Sun
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death globally. Although the gut microbiota's role in the antitumor efficacy of many cancers has been revealed, its involvement in the response to gefitinib therapy for LUAD remains unclear. To fill this gap, we conducted a longitudinal study that profiled gut microbiota changes in PC-9 tumor-bearing mice under different treatments,
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The HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-07 Fangfang Yan, Vivian Jiang, Alexa Jordan, Yuxuan Che, Yang Liu, Qingsong Cai, Yu Xue, Yijing Li, Joseph McIntosh, Zhihong Chen, Jovanny Vargas, Lei Nie, Yixin Yao, Heng-Huan Lee, Wei Wang, JohnNelson R. Bigcal, Maria Badillo, Jitendra Meena, Christopher Flowers, Jia Zhou, Zhongming Zhao, Lukas M. Simon, Michael Wang
Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton’s tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated
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GPR68-ATF4 signaling is a novel prosurvival pathway in glioblastoma activated by acidic extracellular microenvironment Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-31 Charles H. Williams, Leif R. Neitzel, Jessica Cornell, Samantha Rea, Ian Mills, Maya S. Silver, Jovanni D. Ahmad, Konstantin G. Birukov, Anna Birukova, Henry Brem, Betty Tyler, Eli E. Bar, Charles C. Hong
Glioblastoma multiforme (GBM) stands as a formidable challenge in oncology because of its aggressive nature and severely limited treatment options. Despite decades of research, the survival rates for GBM remain effectively stagnant. A defining hallmark of GBM is a highly acidic tumor microenvironment, which is thought to activate pro-tumorigenic pathways. This acidification is the result of altered
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Decoding leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-30 Jianche Liu, Penglei Jiang, Zezhen Lu, Zebin Yu, Pengxu Qian
Leukemias are refractory hematological malignancies, characterized by marked intrinsic heterogeneity which poses significant obstacles to effective treatment. However, traditional bulk sequencing techniques have not been able to effectively unravel the heterogeneity among individual tumor cells. With the emergence of single-cell sequencing technology, it has bestowed upon us an unprecedented resolution
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Targeting focal adhesion kinase boosts immune response in KRAS/LKB1 co-mutated lung adenocarcinoma via remodeling the tumor microenvironment Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-30 Meng Qiao, Fei Zhou, Xinyu Liu, Tao Jiang, Haowei Wang, Xuefei Li, Chao Zhao, Lei Cheng, Xiaoxia Chen, Shengxiang Ren, Zaiqi Wang, Caicun Zhou
KRAS mutation is one of the most common oncogenic drivers in NSCLC, however, the response to immunotherapy is heterogeneous owing to the distinct co-occurring genomic alterations. KRAS/LKB1 co-mutated lung adenocarcinoma displays poor response to PD-1 blockade whereas the mechanism remains undetermined. We explored the specific characteristics of tumor microenvironment (TME) in KL tumors using syngeneic
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Cancer metabolism and carcinogenesis Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-29 Jianqiang Yang, Chloe Shay, Nabil F. Saba, Yong Teng
Metabolic reprogramming is an emerging hallmark of cancer cells, enabling them to meet increased nutrient and energy demands while withstanding the challenging microenvironment. Cancer cells can switch their metabolic pathways, allowing them to adapt to different microenvironments and therapeutic interventions. This refers to metabolic heterogeneity, in which different cell populations use different
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A novel AML1-ETO/FTO positive feedback loop promotes leukemogenesis and Ara-C resistance via stabilizing IGFBP2 in t(8;21) acute myeloid leukemia Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-24 Wei Zhou, Siying Li, Hong Wang, Jingfeng Zhou, Shuyi Li, Guofeng Chen, Wei Guan, Xianli Fu, Clara Nervi, Li Yu, Yonghui Li
t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities in acute myeloid leukemia (AML), leading to the generation of the fusion protein AML1-ETO. Despite t(8;21) AML being considered as a subtype with a favorable prognosis, approximately 30–50% of patients experience drug resistance and subsequent relapse. N6-methyladenosine (m6A) is demonstrated to be involved in the development of
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METTL1 mediated tRNA m7G modification promotes leukaemogenesis of AML via tRNA regulated translational control Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-24 Pan Zhao, Lin Xia, Dan Chen, Wei Xu, Huanping Guo, Yinying Xu, Bingbing Yan, Xiao Wu, Yuxia Li, Yunfang Zhang, Xi Zhang
RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4 have been confirmed an oncogene role in multiple cancers. However, the functions and molecular mechanisms of METTL1/WDR4 in acute myeloid leukemia (AML) remain to be determined. METTL1/WDR4 expression levels were
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Correction: Breast cancer heterogeneity and its implication in personalized precision therapy Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-23 Liantao Guo, Deguang Kong, Jianhua Liu, Ling Zhan, Lan Luo, Weijie Zheng, Qingyuan Zheng, Chuang Chen, Shengrong Sun
Correction: Experimental Hematology & Oncology (2023) 12:3 https://doi.org/10.1186/s40164-022-00363-1 In the Funding secion of this article [1], the grant number relating to National Natural Science Foundation of China was given incorrectly as No.8210114078 and should have been No.82103671. Funding This work was funded by the National Natural Science Foundation of China (Grant No.82103671). The original
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Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-22 Qi Zhao, Hong Zong, Pingping Zhu, Chang Su, Wenxue Tang, Zhenzhen Chen, Shuiling Jin
Cancer immunotherapy has emerged as a promising strategy in the treatment of colorectal cancer, and relapse after tumor immunotherapy has attracted increasing attention. Cancer stem cells (CSCs), a small subset of tumor cells with self-renewal and differentiation capacities, are resistant to traditional therapies such as radiotherapy and chemotherapy. Recently, CSCs have been proven to be the cells
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ZMIZ2 facilitates hepatocellular carcinoma progression via LEF1 mediated activation of Wnt/β-catenin pathway Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-22 Yang Ding, Yumei Ning, Hui Kang, Yuan Yuan, Kun Lin, Chun Wang, Yun Yi, Jianghua He, Lurao Li, Xingxing He, Ying Chang
Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high lethality rate. ZMIZ2 is a transcriptional co-activator implicated in various human diseases. However, the role and molecular mechanism of ZMIZ2 in HCC remains to be elucidated. The expression and prognostic value of ZMIZ2 in HCC was excavated from public databases and explored by bioinformatic analysis. Then the expression
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Outcomes of allogeneic hematopoietic stem cell transplantation in R/R DLBCL patients with failure of CAR-T therapy Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-16 Mengya Cong, Sicheng Ai, Liqing Kang, Mao Jin, Ying Zhu, Caixia Li, Zhengming Jin, Lei Yu, Depei Wu, Haiwen Huang
From October 2017 to June 2022, we retrospectively report outcomes of R/R DLBCL patients with failure of CAR-T therapy, then receiving allo-HSCT. Among 10 patients, 5 were males and 5 females, with a median age of 43.5 (27–52) years. All patients were diagnosed refractory/relapsed diffuse large B cell lymphoma. The median time from CAR-T treatment to transplantation was 84.5 (31–370) days. The median
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The roles of tissue resident macrophages in health and cancer Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-16 Minmin Cao, Zihao Wang, Wanying Lan, Binghua Xiang, Wenjun Liao, Jie Zhou, Xiaomeng Liu, Yiling Wang, Shichuan Zhang, Shun Lu, Jinyi Lang, Yue Zhao
As integral components of the immune microenvironment, tissue resident macrophages (TRMs) represent a self-renewing and long-lived cell population that plays crucial roles in maintaining homeostasis, promoting tissue remodeling after damage, defending against inflammation and even orchestrating cancer progression. However, the exact functions and roles of TRMs in cancer are not yet well understood
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Molecular profiling of biliary tract cancers reveals distinct genomic landscapes between circulating and tissue tumor DNA Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-08 Clémence Astier, Carine Ngo, Léo Colmet-Daage, Virginie Marty, Olivia Bawa, Claudio Nicotra, Maud Ngo-Camus, Antoine Italiano, Christophe Massard, Jean-Yves Scoazec, Cristina Smolenschi, Michel Ducreux, Antoine Hollebecque, Sophie Postel-Vinay
Biliary tract cancers (BTCs) are heterogeneous malignancies with dismal prognosis due to tumor aggressiveness and poor response to limited current therapeutic options. Tumor exome profiling has allowed to successfully establish targeted therapeutic strategies in the clinical management of cholangiocarcinoma (CCA). Still, whether liquid biopsy profiling could inform on BTC biology and patient management
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Recent updates on central nervous system prophylaxis in patients with high-risk diffuse large B-cell lymphoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-03 Bernard Ji Guang Chua, Chen Ee Low, Chun En Yau, Ya Hwee Tan, Jianbang Chiang, Esther Wei Yin Chang, Jason Yongsheng Chan, Eileen Yi Ling Poon, Nagavalli Somasundaram, Mohamed Farid Bin Harunal Rashid, Miriam Tao, Soon Thye Lim, Valerie Shiwen Yang
The use of central nervous system (CNS) prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) remains controversial. Although uncommon, CNS relapses are invariably fatal in this otherwise curable disease. Accurate identification of patients at risk and the optimal approach to CNS prophylaxis therefore remains an area of unmet need. The existing literature, largely retrospective in nature
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Targeting ST8SIA6-AS1 counteracts KRASG12C inhibitor resistance through abolishing the reciprocal activation of PLK1/c-Myc signaling Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-16 Yafang Wang, Mingyue Yao, Cheng Li, Kexin Yang, Xiaolong Qin, Lansong Xu, Shangxuan Shi, Chengcheng Yu, Xiangjun Meng, Chengying Xie
KRASG12C inhibitors (KRASG12Ci) AMG510 and MRTX849 have shown promising efficacy in clinical trials and been approved for the treatment of KRASG12C-mutant cancers. However, the emergence of therapy-related drug resistance limits their long-term potential. This study aimed to identify the critical mediators and develop overcoming strategies. By using RNA sequencing, RT-qPCR and immunoblotting, we identified
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ProNGF promotes brain metastasis through TrkA/EphA2 induced Src activation in triple negative breast cancer cells Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-10 Julien Cicero, Sarah Trouvilliez, Martine Palma, Gaetan Ternier, Laurine Decoster, Eloise Happernegg, Nicolas Barois, Alexandre Van Outryve, Lucie Dehouck, Roland P. Bourette, Eric Adriaenssens, Chann Lagadec, Cagatay Mehmet Tarhan, Dominique Collard, Zied Souguir, Elodie Vandenhaute, Grégory Maubon, François Sipieter, Nicolas Borghi, Fumitaka Shimizu, Takashi Kanda, Paolo Giacobini, Fabien Gosselet
Triple-Negative Breast Cancer is particularly aggressive, and its metastasis to the brain has a significant psychological impact on patients' quality of life, in addition to reducing survival. The development of brain metastases is particularly harmful in triple-negative breast cancer (TNBC). To date, the mechanisms that induce brain metastasis in TNBC are poorly understood. Using a human blood–brain
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The role of pyroptosis and gasdermin family in tumor progression and immune microenvironment Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-08 Mengyuan Li, Ping Jiang, Yuhan Yang, Liting Xiong, Shuhua Wei, Junjie Wang, Chunxiao Li
Pyroptosis, an inflammatory programmed cell death, distinguishes itself from apoptosis and necroptosis and has drawn increasing attention. Recent studies have revealed a correlation between the expression levels of many pyroptosis-related genes and both tumorigenesis and progression. Despite advancements in cancer treatments such as surgery, radiotherapy, chemotherapy, and immunotherapy, the persistent
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Antitumor effect of a small-molecule inhibitor of KRASG12D in xenograft models of mucinous appendicular neoplasms Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-08 Mari C. Vázquez-Borrego, Melissa Granados-Rodríguez, Florina I. Bura, Ana Martínez-López, Blanca Rufián-Andújar, Francisca Valenzuela-Molina, Lidia Rodríguez-Ortiz, Sergio Haro-Yuste, Ana Moreno-Serrano, Rosa Ortega-Salas, Rafael Pineda-Reyes, Carmen Michán, José Alhama, Antonio Romero-Ruiz, Álvaro Arjona-Sánchez
Pseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive surgery, aimed at removing all visible tumors. However, a high percentage of patients relapse, with subsequent progression and death. Recently, there has been an increase in therapies that target mutated oncogenic proteins. In this sense
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A bile-based microRNA signature for differentiating malignant from benign pancreaticobiliary disease Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-01 Mireia Mato Prado, Jisce R. Puik, Leandro Castellano, Elena López-Jiménez, Daniel S. K. Liu, Laura L. Meijer, Tessa Y. S. Le Large, Eleanor Rees, Niccola Funel, Shivan Sivakumar, Stephen P. Pereira, Geert Kazemier, Babs M. Zonderhuis, Joris I. Erdmann, Rutger-Jan Swijnenburg, Andrea Frilling, Long R. Jiao, Justin Stebbing, Elisa Giovannetti, Jonathan Krell, Adam E. Frampton
Differentiating between pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) is crucial for the appropriate course of treatment, especially with advancements in the role of neoadjuvant chemotherapies for PDAC, compared to CCA. Furthermore, benign pancreaticobiliary diseases can mimic malignant disease, and indeterminate lesions may require repeated investigations to achieve a diagnosis
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Upregulated PARP1 confers breast cancer resistance to CDK4/6 inhibitors via YB-1 phosphorylation Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-30 Chuntao Quan, Zhijie Wu, Juan Xiong, Manqing Li, Yu Fu, Jiaying Su, Yue Wang, Lvwen Ning, Deju Zhang, Ni Xie
Cyclic-dependent kinase (CDK) 4/6 kinases, as the critical drivers of the cell cycle, are involved in the tumor progression of various malignancies. Pharmacologic inhibitors of CDK4/6 have shown significant clinical prospects in treating hormone receptor-positive and human epidermal growth factor receptor-negative (HR + /HER2-) breast cancer (BC) patients. However, acquired resistance to CDK4/6 inhibitors
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Immune checkpoint inhibitors for multiple myeloma immunotherapy Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-28 Zhaoyun Liu, Xintong Xu, Hui Liu, Xianghong Zhao, Chun Yang, Rong Fu
Multiple myeloma (MM) is related to immune disorders, recent studys have revealed that immunotherapy can greatly benefit MM patients. Immune checkpoints can negatively modulate the immune system and are closely associated with immune escape. Immune checkpoint-related therapy has attracted much attention and research in MM. However, the efficacy of those therapies need further improvements. There need
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Single VHH-directed BCMA CAR-NK cells for multiple myeloma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-27 Quan Ren, Yingling Zu, Hongchang Su, Qiumei Lu, Bin Xiang, Yanping Luo, Jishuai Zhang, Yongping Song
Natural killer (NK) cells are promising alternatives for the production of “off-the-shelf” CAR products, posing a lower risk of cytokine release syndrome (CRS) than CAR-T cells. We synthesized four single VHH-directed anti-BCMA CARs, incorporating various intracellular regions (2B4 versus CD28) and hinge domains (CD28 versus IgG1) and ectopically producing IL-15. NK cells derived from peripheral blood
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Deciphering tumor-infiltrating dendritic cells in the single-cell era Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-27 Qingyu Huang, Fuhao Wang, Di Hao, Xinyu Li, Xiaohui Li, Tianyu Lei, Jinbo Yue, Chao Liu
Dendritic cells (DCs) serve as a pivotal link connecting innate and adaptive immunity by processing tumor-derived antigens and activating T cells. The advent of single-cell sequencing has revolutionized the categorization of DCs, enabling a high-resolution characterization of the previously unrecognized diversity of DC populations infiltrating the intricate tumor microenvironment (TME). The application
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Molecular characterization of the CXCR4 / CXCR7 axis in germ cell tumors and its targetability using nanobody-drug-conjugates Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-23 Gamal A. Wakileh, Philipp Bierholz, Mara Kotthoff, Margaretha A. Skowron, Felix Bremmer, Alexa Stephan, Stephanie M. Anbuhl, Raimond Heukers, Martine J. Smit, Philipp Ströbel, Daniel Nettersheim
Being stimulated by the chemokine CXCL12, the CXCR4 / CXCR7 cascade is involved in tumor proliferation, migration, and metastasis. The interaction between CXCL12, secreted by cells from the microenvironment, and its receptors is complex and has been ascribed to promote chemotherapy resistance. However, the role of this signaling axis and its targetability in germ cell tumors (GCT) is not fully understood
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CRISPR/Cas9 system: recent applications in immuno-oncology and cancer immunotherapy Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-14 Chen Chen, Zehua Wang, Yanru Qin
Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is essentially an adaptive immunity weapon in prokaryotes against foreign DNA. This system inspires the development of genome-editing technology in eukaryotes. In biomedicine research, CRISPR has offered a powerful platform to establish tumor-bearing models and screen potential targets in the immuno-oncology
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Downregulation of pro-surfactant protein B contributes to the recurrence of early-stage non-small cell lung cancer by activating PGK1-mediated Akt signaling Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-09 Hao Luo, Qing Li, Ren-Tao Wang, Liang Zhang, Wei Zhang, Meng-Sheng Deng, Yuan-Yuan Luo, Xintong Ji, Yongheng Wen, Xuan-Rui Zhou, Bo Xu, Dong Wang, Bin Hu, Hua Jin, Cheng-Xiong Xu
Recurrence is one of the main causes of treatment failure in early-stage non-small cell lung cancer (NSCLC). However, there are no predictors of the recurrence of early-stage NSCLC, and the molecular mechanism of its recurrence is not clear. In this study, we used clinical sample analysis to demonstrate that low levels of expression of precursor surfactant protein B (pro-SFTPB) in primary NSCLC tissue
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The current landscape of using direct inhibitors to target KRASG12C-mutated NSCLC Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-04 Firas Batrash, Mahmoud Kutmah, Jun Zhang
Mutation in KRAS protooncogene represents one of the most common genetic alterations in NSCLC and has posed a great therapeutic challenge over the past ~ 40 years since its discovery. However, the pioneer work from Shokat’s lab in 2013 has led to a recent wave of direct KRASG12C inhibitors that utilize the switch II pocket identified. Notably, two of the inhibitors have recently received US FDA approval
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Chinese expert consensus on Bruton tyrosine kinase inhibitors in the treatment of B-cell malignancies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-10-16 Yuqin Song, Shang-Ju Wu, Zhixiang Shen, Donglu Zhao, Thomas Sau Yan Chan, Huiqiang Huang, Lugui Qiu, Jianyong Li, Tran-der Tan, Jun Zhu, Yongping Song, Wei-Han Huang, Weili Zhao, Herman Sung Yu Liu, Wei Xu, Naizhi Chen, Jun Ma, Cheng-Shyong Chang, Eric Wai Choi Tse
Targeted therapy with Bruton tyrosine kinase (BTK) inhibitors have revolutionized the treatment of patients with various B-cell malignancies. BTK inhibitors such as ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib have shown good clinical efficacy and better safety profiles than those of traditional chemotherapy and chemoimmunotherapy regimens. Multiple studies on new BTK inhibitors are ongoing
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New insight into circRNAs: characterization, strategies, and biomedical applications Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-10-12 Xin-Yi Feng, Shun-Xin Zhu, Ke-Jia Pu, Heng-Jing Huang, Yue-Qin Chen, Wen-Tao Wang
Circular RNAs (circRNAs) are a class of covalently closed, endogenous ncRNAs. Most circRNAs are derived from exonic or intronic sequences by precursor RNA back-splicing. Advanced high-throughput RNA sequencing and experimental technologies have enabled the extensive identification and characterization of circRNAs, such as novel types of biogenesis, tissue-specific and cell-specific expression patterns
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Targeting CD22 for B-cell hematologic malignancies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-10-11 Jia Xu, Wenjing Luo, Chenggong Li, Heng Mei
CD19-targeted chimeric receptor antigen (CAR)-T cell therapy has shown remarkable clinical efficacy in the treatment of relapsed or refractory (R/R) B-cell malignancies. However, 30%–60% of patients eventually relapsed, with the CD19-negative relapse being an important hurdle to sustained remission. CD22 expression is independent of CD19 expression in malignant B cells. Consequently, CD22 is a potential
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Regulatory T cells contribute to the immunosuppressive phenotype of neutrophils in a mouse model of chronic lymphocytic leukemia Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-10-10 Agnieszka Goral, Marta Sledz, Aneta Manda-Handzlik, Adrianna Cieloch, Alicja Wojciechowska, Mieszko Lachota, Agnieszka Mroczek, Urszula Demkow, Radoslaw Zagozdzon, Katarzyna Matusik, Malgorzata Wachowska, Angelika Muchowicz
Impaired neutrophil activity is an important issue in chronic lymphocytic leukemia (CLL), as it contributes to a dysfunctional immune response leading to life-threatening infections in patients. Some features typical of CLL neutrophils, e.g., the B-cell-supportive secretion profile, have already been described. However, most of these studies were performed on cells isolated from peripheral blood. It
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CRISPR/Cas9-mediated knockout of intracellular molecule SHP-1 enhances tumor-killing ability of CD133-targeted CAR T cells in vitro Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-10-06 Ming Liu, Linlin Zhang, Mingtian Zhong, Yihao Long, Wenhui Yang, Ting Liu, Xingxu Huang, Xiaodong Ma
CAR T cell therapy has been successfully used in the treatment of hematological malignancies, and the strategy that deletion of inhibitory receptor on the CAR T cell surface, such as PD-1, greatly enhance the antitumor effects. Here, we describe a one-step electroporation for the co-transfection of Cas9:sgRNA and CAR plasmids on primary T cells to demonstrate the effect of SHP-1 deletion in CAR T cells
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Identification of a novel NPM1 mutation in acute myeloid leukemia Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-10-04 Yiyi Yao, Xiangjie Lin, Chen Wang, Ying Gu, Jie Jin, Yinghui Zhu, Huafeng Wang
Nucleophosmin (NPM1) is a widely expressed nucleocytoplasmic shuttling protein with prominent nucleolar localization. It is estimated that 25–35% of adult patients with acute myeloid leukemia (AML) carry NPM1 mutations. The classic NPM1 type A mutation occurs in exon 12, which accounts for 75–80% of adult patients with NPM1-mutated AML. It produces an additional leucine and valine-rich nuclear export
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Correction to: Bispecific antibodies and dual-targeting CAR-T cells for multiple myeloma: latest updates from the 2023 ASCO annual meeting Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-10-03 Jiangxue Hou, Yufu Li, Quande Lin
Experimental Hematology & Oncology (2023) 12:74 https://doi.org/10.1186/s40164-023-00436-9 After online publication of the article1, the authors noticed Table 1 and 2 should have been published in the main article were inadvertently submitted and processed as Supplementary files. The correct tables are published with this erratum. Table 1 Properties of bispecific antibodies for multiple myelomaFull
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Targeting and cytotoxicity of chimeric antigen receptor T cells grafted with PD1 extramembrane domain Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-09-30 Ang Zhang, Shenyu Wang, Yao Sun, Yikun Zhang, Long Zhao, Yang Yang, Yijian Zhang, Lei Xu, Yangyang Lei, Jie Du, Hu Chen, Lian Duan, Mingyi He, Lintao Shi, Lei Liu, Quanjun Wang, Liangding Hu, Bin Zhang
Immunosuppression induced by programmed cell death protein 1 (PD1) presents a significant constraint on the effectiveness of chimeric antigen receptor (CAR)-T therapy. The potential of combining PD1/PDL1 (Programmed cell death 1 ligand 1) axis blockade with CAR-T cell therapy is promising. However, developing a highly efficient and minimally toxic approach requires further exploration. Our attempt
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Role of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-09-28 Mengwei Zhang, Jinkai Liu, Qiang Xia
Immunotherapy has emerged as an effective treatment for various types of cancers. Recent studies have highlighted a significant correlation between the gut microbiome and patients’ response to immunotherapy. Several characteristics of the gut microbiome, such as community structures, taxonomic compositions, and molecular functions, have been identified as crucial biomarkers for predicting immunotherapy
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Focal adhesion kinase: from biological functions to therapeutic strategies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-09-25 Ximin Tan, Yuheng Yan, Bin Song, Shuangli Zhu, Qi Mei, Kongming Wu
Focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, is a vital participant in primary cellular functions, such as proliferation, survival, migration, and invasion. In addition, FAK regulates cancer stem cell activities and contributes to the formation of the tumor microenvironment (TME). Importantly, increased FAK expression and activity are strongly associated with unfavorable
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The PTX3/TLR4 autocrine loop as a novel therapeutic target in triple negative breast cancer Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-09-25 Arianna Giacomini, Marta Turati, Elisabetta Grillo, Sara Rezzola, Gaia Cristina Ghedini, Ander Churruca Schuind, Eleonora Foglio, Federica Maccarinelli, Jessica Faletti, Serena Filiberti, Angela Chambery, Mariangela Valletta, Laura Melocchi, Stephanie Gofflot, Barbara Chiavarina, Andrei Turtoi, Marco Presta, Roberto Ronca
The pattern recognition receptor long pentraxin-3 (PTX3) plays conflicting roles in cancer by acting as an oncosuppressor or as a pro-tumor mediator depending on tumor context. Triple negative breast cancer (TNBC) represents the most aggressive histotype of breast cancer, characterized by the lack of efficacious therapeutic targets/approaches and poor prognosis. Thus, the characterization of new molecular
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Modelling acquired resistance to DOT1L inhibition exhibits the adaptive potential of KMT2A-rearranged acute lymphoblastic leukemia Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-09-22 Pauline Schneider, Nicholas T. Crump, Susan T.C.J.M. Arentsen-Peters, Alastair L. Smith, Rico Hagelaar, Fabienne R.S. Adriaanse, Romy S. Bos, Anja de Jong, Stefan Nierkens, Bianca Koopmans, Thomas A. Milne, Rob Pieters, Ronald W. Stam
In KMT2A-rearranged acute lymphoblastic leukemia (ALL), an aggressive malignancy, oncogenic KMT2A-fusion proteins inappropriately recruit DOT1L to promote leukemogenesis, highlighting DOT1L as an attractive therapeutic target. Unfortunately, treatment with the first-in-class DOT1L inhibitor pinometostat eventually leads to non-responsiveness. To understand this we established acquired pinometostat
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Recent advances and future perspectives in the therapeutics of prostate cancer Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-09-22 Ganji Lakshmi Varaprasad, Vivek Kumar Gupta, Kiran Prasad, Eunsu Kim, Mandava Bhuvan Tej, Pratik Mohanty, Henu Kumar Verma, Ganji Seeta Rama Raju, LVKS Bhaskar, Yun Suk Huh
Prostate cancer (PC) is one of the most common cancers in males and the fifth leading reason of death. Age, ethnicity, family history, and genetic defects are major factors that determine the aggressiveness and lethality of PC. The African population is at the highest risk of developing high-grade PC. It can be challenging to distinguish between low-risk and high-risk patients due to the slow progression
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A novel CAR-T cell product targeting CD74 is an effective therapeutic approach in preclinical mantle cell lymphoma models Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-09-22 Wing Keung Chan, Jessica Williams, Kinnari Sorathia, Betsy Pray, Kaled Abusaleh, Zehua Bian, Archisha Sharma, Ian Hout, Shamama Nishat, Walter Hanel, Shelby L. Sloan, Aneeq Yasin, Nathan Denlinger, Xiaoli Zhang, Natarajan Muthusamy, Sumithira Vasu, Marcos de Lima, Yiping Yang, Robert Baiocchi, Lapo Alinari
Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma subtype which remains incurable despite multimodal approach including chemoimmunotherapy followed by stem cell transplant, targeted approaches such as the BTK inhibitor ibrutinib, and CD19 chimeric antigen receptor (CAR) T cells. CD74 is a nonpolymorphic type II integral membrane glycoprotein identified as an MHC class II chaperone and
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Preclinical activity of selinexor in combination with eribulin in uterine leiomyosarcoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-09-15 Sonam Mittal, Ishaque Pulikkal Kadamberi, Hua Chang, Feng Wang, Sudhir Kumar, Shirng-Wern Tsaih, Christopher J. Walker, Pradeep Chaluvally-Raghavan, John Charlson, Yosef Landesman, Sunila Pradeep
Leiomyosarcoma (LMS) is a rare soft tissue sarcoma (STS) that begins in smooth muscle tissue and most often initiates in the abdomen or uterus. Compared with other uterine cancers, uterine LMS (ULMS) is an aggressive tumor with poor prognosis and a high risk of recurrence and death, regardless of the stage at presentation. Selinexor is a first-in-class selective inhibitor of nuclear export (SINE) compound