Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy, primarily comprising intrahepatic (iCCA) and extrahepatic (eCCA) subtypes. Reconciling the variability between iCCAs and eCCAs in clinical trials remains a challenge, largely due to the inadequate understanding of their shared and subtype-specific cellular heterogeneity. We aim to address this issue using single-cell and spatially resolved

Frailty is more prevalent among venous thromboembolism (VTE) patients. However, the relationship between long‐term VTE risk and frailty remained unexplored. This study included 315 523 participants recruited from UK Biobank between 2006 and 2010. Frailty status of participants at recruitment was evaluated by physical frailty and frailty index. The association between frailty and long‐term risk of VTE

Mutations in TP53 are mutually exclusive with other known drivers of myeloid transformation and define a distinct molecular subtype within de novo Acute Myeloid Leukemia (AML) that is associated with a complex karyotype, resistance to chemotherapy, and poor prognosis. Although TP53 defects are rare in de novo AML, biallelic mutations are a defining molecular feature of erythroleukemia. The genetic

Platelet shape and volume changes are early mechanical events contributing to platelet activation and thrombosis. Here, we identify single-nucleotide polymorphisms in Leucine-Rich Repeat Containing 8 (LRRC8) protein subunits that form the Volume-Regulated Anion Channel (VRAC) which are independently associated with altered mean platelet volume. LRRC8A is required for functional VRAC in megakaryocytes

Disease-defining signatures in lymphomas, driven by intricate molecular mechanisms, have advanced molecular taxonomies, refined classification, and may guide clinical management; however, the role of these signatures in driving disease hallmarks including subtype-specific organotropism remains largely unexplored. Primary mediastinal large B-cell lymphoma (PMBCL) is an exemplary lymphoma characterized

In inflammation, circulating neutrophils indirectly damage the skeleton by inducing formation of bone-resorbing osteoclasts. However, neutrophil progenitors in marrow have no known physiological function. A bone-protective role for the neutrophil lineage was recently suggested when a profound defect in bone structure was observed in mice with neutropenia due to Granulocyte Colony Stimulating Factor

The Duffy-null phenotype is prevalent in individuals of African and Middle Eastern ancestry. It is associated with lower absolute neutrophil counts (ANCs), which are termed Duffy-null associated neutrophil counts (DANCs) [1]. The Duffy blood group consists of two main antigens, Fya and Fyb, and is encoded by the atypical chemokine receptor 1 (ACKR1) gene. Homozygosity for a SNP (rs2814778; T>C; CC)

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder classified into three recognized clinical subtypes—idiopathic plasmacytic lymphadenopathy (IPL), TAFRO, and NOS. Although clinical criteria are available for subtyping, diagnostically challenging cases with overlapping histopathological features highlight the need for an improved classification system integrating

In the United States, 22 000 splenectomies are performed annually [1] for various conditions. Splenectomy has been linked to overwhelming sepsis and more recently to thromboembolic events (TEE) [2-5]. Danish national registry studies documented the increased occurrence of TEE postsplenectomy; however, earlier studies were restricted to males and later ones, including two Danish studies, did not discriminate

The extracellular matrix (ECM), closely linked to the dynamic changes in the tumor microenvironment (TME), plays a critical role in modulating tumor immunity. The dual role of the ECM in tumor progression, encompassing both promotion and inhibition, is attributed to its components influencing immune cell activation, migration, and infiltration. This mechanism is intricately connected with the efficacy

Luspatercept, an erythroid maturation agent promoting late-stage erythropoiesis, has been approved for the treatment of anemia in adult patients with transfusion-dependent β-thalassemia (TDT) since 2019. The marketing authorization was based on data from the phase 3 BELIEVE trial which showed that 21.4% of 224 patients had at least a 33% reduction in their transfusion requirement compared to 4.5% of

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is pivotal for hematological malignancies but faces challenges in delayed platelet engraftment, poor graft function (PGF), and bleeding risks. Hetrombopag, a thrombopoietin receptor agonist, was evaluated to enhance platelet recovery posttransplant. Patients undergoing allo‐HSCT were randomized on Day 3 Post‐Infusion into low‐dose (2.5

AL amyloidosis is a serious disease characterized by the deposition of immunoglobulin light chains in multiple organs. Renal involvement occurs in up to 70% of patients, but only a minority require dialysis before initiating anti-clonal treatment. Understanding the occurrence of end-stage organ damage is crucial to pave the way for reversing deposition. Currently, there is no detailed analysis available

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The combination of anti-thymocyte globulin (ATG) and posttransplant cyclophosphamide (PTCy) appears to be a potentially effective graft-versus-host disease (GVHD) prevention strategy for haploidentical transplantation. However, the majority of the evidence originated from retrospective studies without uniform protocols. Our previous findings indicated that 10 mg/kg ATG plus low-dose PTCy could decrease

The phosphoinositide 3-kinase (PI3K) pathway remains a potent drug target in hematological malignancies despite the challenges that have affected clinical drug development, particularly unpredictable toxicity, and inherent/acquired drug resistance. Herein, we tested the activity of a novel PI3Kδ selective, non-ATP competitive inhibitor, roginolisib (IOA-244), in hematological malignancies including

Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor outcomes following B-cell maturation antigen (BCMA)-targeted CAR-T therapy, yet its impact on treatment-related toxicity remains unclear. This study evaluates the impact of active EMD on toxicity, efficacy, and survival in patients with MM treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel)

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Dysregulated megakaryocytopoiesis contributes to reduced platelet counts in immune thrombocytopenic purpura (ITP), yet the mechanism remains elusive. Although 5-hydroxytryptamine receptor 7 (5-HTR7) has been implicated in megakaryocyte (MK) biology, its pathogenic involvement in ITP is undefined. This study investigated the impact of 5-HTR7 on MK maturation in ITP using flow cytometry, immunofluorescence

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The intensity of the conditioning regimen in hematopoietic stem cell transplantation (HSCT) correlates with the risk of relapse, however its potential benefit may be outweighed by the associated risk of toxicity. The addition of total marrow irradiation (TMI) to myeloablative conditioning provides an opportunity to increase intensity with minimal additional toxicity. In this phase 2 clinical trial

People with chronic lymphocytic leukemia (CLL) have a median age at diagnosis of around 70 years [1]. With an average time to first treatment of 4–5 years from diagnosis, it is estimated that a third of all people with CLL will be ≥ 80 years old when they become symptomatic and receive frontline therapy [1]. People ≥ 80 years old often have comorbidities and unfavorable disease characteristics (like

Nodal follicular helper T-cell (TFH) lymphoma of the angioimmunoblastic (AITL) subtype has a dismal prognosis. Using whole-exome sequencing (n = 124), transcriptomic (n = 78), and methylation (n = 40) analysis, we identified recurrent mutations in known epigenetic drivers (TET2, DNMT3A, IDH2R172) and novel ones (TET3, KMT2D). TET2, IDH2R172, DNMT3A co-mutated AITLs had poor prognosis (p < 0.0001).

Anemia of inflammation (AI) is the second most common form of anemia and is prevalent in patients with chronic inflammatory states, such as infection, autoimmunity, and cancer. Interleukin 6 (IL6) is well-known to induce the iron-sequestering hormone hepcidin, which results in iron-restricted anemia. The contributions of other pro-inflammatory cytokines such as tumor necrosis factor-α (TNFα) and interferon-γ

A 57-year-old Spanish woman was referred for investigation of chronic anemia. Her mother and grandmother also had a history of anemia. There was no jaundice and no abdominal pain or tenderness, but abdominal ultrasonography showed homogeneous splenomegaly, the spleen measuring 14.2 cm. She had required a transfusion on one occasion when the hemoglobin concentration (Hb) fell to 71 g/L. Her blood count

Correction to: Journal of Hematology & Oncology (2018) 11:95. https://doi.org/10.1186/s13045-018-0638-9 During figure preparation, an incorrect representative image was included in Figs. 1e, S5B, and S6C. These errors occurred during figure assembly and do not affect the results or conclusions of the study. The corrected figures have been provided. The authors apologize for the errors and any confusion

Menin inhibitors, which target the KMT2A-menin protein-protein interaction to inhibit blasts proliferation and induce differentiation, have demonstrated potential effects on acute leukemia subtypes characterized by overexpression of HOXA gene cluster and MEIS1 (including KMT2A rearrangements, NPM1 mutations, NUP98 rearrangements and other genetic alterations). Following the promising outcomes of the

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An acute inflammatory response to infection or sterile injury involves an adequate activation and recruitment of leukocytes. Activation of β2-integrins is required for neutrophil recruitment and is also mandatory for various neutrophil cell-intrinsic functions. GTPases are key regulators of the actin cytoskeleton and are required for β2‐integrin activation. MyosinIXb (Myo9b), a Rho GTPase-activating

Monoclonal antibodies targeting CD38 are a therapeutic mainstay in multiple myeloma (MM). Although they have contributed to improved outcomes, most patients still experience disease relapse, and little is known about tumor-intrinsic mechanisms of resistance to these drugs. Antigen escape has been implicated as a mechanism of tumor-cell evasion in immunotherapy. Yet, it is unknown whether MM cells can

TET2 is among the most commonly mutated genes in both clonal hematopoiesis and myeloid malignancies; thus, the ability to identify selective dependencies in TET2-deficient cells has broad translational significance. Here, we identify regulators of Tet2 knockout (KO) hematopoietic stem and progenitor cell (HSPC) expansion using an in vivo CRISPR-Cas9 KO screen, in which nucleotide barcoding enabled

Developing anti–factor VIII (FVIII) inhibitory antibodies (inhibitors) are a significant complication of FVIII protein replacement therapy in hemophilia A. Our previous study demonstrated that follicular helper T (TFH) cells play a critical role in FVIII inhibitor development. Follicular regulatory T (TFR) cells are a subset of Foxp3+ T cells recently identified in the germinal center that can modulate

Two doses of subcutaneous blinatumomab in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia were identified as preliminary recommended phase 2 doses, based on the dose-escalation phase of this multicentre single-arm, phase 1/2 trial. Here, we aim to further study the safety, activity, and pharmacokinetics of these doses in all participants who have received them, including those