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利用急性髓细胞性白血病中干细胞自我更新途径的治疗诊断策略。

Theragnostic strategies harnessing the self-renewal pathways of stem-like cells in the acute myeloid leukemia.

机构信息

KIIT School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT-DU), Bhubaneswar, Odisha, India.

Department of Pharmacology, DIPSAR, Delhi Pharmaceutical Sciences and Research University, New Delhi, India.

出版信息

Crit Rev Oncol Hematol. 2022 Sep;177:103753. doi: 10.1016/j.critrevonc.2022.103753. Epub 2022 Jul 5.

Abstract

Acute myelogenous leukemia (AML) is a genetically heterogeneous and aggressive cancer of the Hematopoietic Stem/progenitor cells. It is distinguished by the uncontrollable clonal growth of malignant myeloid stem cells in the bone marrow, venous blood, and other body tissues. AML is the most predominant of leukemias occurring in adults (25%) and children (15-20%). The relapse after chemotherapy is a major concern in the treatment of AML. The overall 5-year survival rate in young AML patients is about 40-45% whereas in the elderly patients it is less than 10%. Leukemia stem-like cells (LSCs) having the ability to self-renew indefinitely, repopulate and persist longer in the G0/G1 phase play a crucial role in the AML relapse and refractoriness to chemotherapy. Hence, novel treatment strategies and diagnostic biomarkers targeting LSCs are being increasingly investigated. Through this review, we have explored the signaling modulations in the LSCs as the theragnostic targets. The significance of the self-renewal pathways in overcoming the treatment challenges in AML has been highlighted.

摘要

急性髓系白血病(AML)是一种遗传异质性和侵袭性的造血干/祖细胞肿瘤。其特征是恶性髓系干细胞在骨髓、静脉血液和其他身体组织中不受控制地克隆生长。AML 是成人(25%)和儿童(15-20%)中最常见的白血病。化疗后复发是 AML 治疗的主要关注点。年轻 AML 患者的总体 5 年生存率约为 40-45%,而老年患者则低于 10%。具有无限自我更新、重新填充和更长时间停留在 G0/G1 期能力的白血病干细胞样细胞(LSCs)在 AML 复发和对化疗的耐药性中起着至关重要的作用。因此,针对 LSCs 的新型治疗策略和诊断生物标志物正越来越受到关注。通过这篇综述,我们探讨了 LSCs 中的信号转导调控作为治疗和诊断靶点的作用。强调了自我更新途径在克服 AML 治疗挑战方面的重要性。

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