Myelodysplastic syndrome (MDS) is regarded as a spectrum of bone marrow failure disorders that share hemato‐pathological state of cellular dysplasia and cytopenia. The modern treatment of cancers like chemotherapy and radiation therapy sometimes severely pounce on the basic hematopoietic stem/progenitor cellular (HSPC) compartment which gradually disclose the clinical symptoms of MDS. The present study involves flowcytometric protein expression analysis of insulin growth factor receptor (IGFR), PI3K‐Akt‐mTOR pathway, the autophagy related proteins (ATG's), the status of antioxidative molecules SOD2 and SDF1 and apoptosis profiling in ethyl‐nitroso‐urea induced myelodysplasia. The redox status that is, reactive oxygen species was estimated with dihydroetidium and the status of mitochondria and lysosomes were checked by Janus green B and neutral red staining respectively, pre and post quercetin treatment in MDS bone marrow. The results revealed the activated IGFR/PI3K/Akt axis in MDS bone marrow but unconventionally both p‐mTOR and autophagy (p‐ATG1, p‐AT6, ATG7, ATG12) was downregulated. Interestingly, post quercetin treatment an upregulation of basal autophagocytosis, reversal of oxidative damage and proper functionality of mitochondria and lysosome was recorded. Taken together, the study hinted that the PI3K‐Akt‐mTOR pathway does not rule over the process of autophagocytosis in HSPC's of MDS bone marrow and the isoflavanoid quercetin remarkably restored autophagocytosis and hematopoietic oxidative status toward normalcy during the progression of myelodysplasia.

中文翻译：

---

槲皮素诱导骨髓增生异常骨髓（包括造血干/祖细胞室）的自噬

骨髓增生异常综合征 (MDS) 被认为是一系列骨髓衰竭疾病，具有细胞发育不良和血细胞减少的血液病理状态。现代癌症治疗如化学疗法和放射疗法有时会严重攻击基本的造血干/祖细胞 (HSPC) 区室，这些区室逐渐揭示 MDS 的临床症状。本研究涉及胰岛素生长因子受体 (IGFR)、PI3K-Akt-mTOR 通路、自噬相关蛋白 (ATG)、抗氧化分子 SOD2 和 SDF1 的状态以及乙基亚硝基脲诱导的细胞凋亡分析骨髓增生异常。氧化还原状态是​​，在 MDS 骨髓中，槲皮素处理前和后，分别通过 Janus 绿 B 和中性红染色检查线粒体和溶酶体的状态，并用 dihydroetidium 估计活性氧。结果显示 MDS 骨髓中激活的 IGFR/PI3K/Akt 轴，但非常规地 p-mTOR 和自噬（p-ATG1、p-AT6、ATG7、ATG12）均下调。有趣的是，槲皮素治疗后基础自噬的上调，氧化损伤的逆转以及线粒体和溶酶体的正常功能被记录下来。综上所述，该研究提示 PI3K-Akt-mTOR 通路并不能支配 HSPC 的自噬过程'