CXCR4 as a therapeutic target in acute myeloid leukemia

IF 12.8 1区医学 Q1 HEMATOLOGY

Leukemia Pub Date : 2024-09-11 DOI:10.1038/s41375-024-02326-3

Jan Korbecki, Mateusz Bosiacki, Patrycja Kupnicka, Katarzyna Barczak, Dariusz Chlubek, Irena Baranowska-Bosiacka

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Abstract

Extensive research on the CXCL12-CXCR4 axis in acute myeloid leukemia (AML) has resulted in the incorporation of novel anti-leukemia drugs targeting this axis into therapeutic strategies. However, despite this progress, a comprehensive and up-to-date review addressing the role of the CXCL12-CXCR4 axis in AML’s oncogenic processes is lacking. In this review, we examine its molecular aspects influencing cancer progression, such as its impact on autonomous proliferation, apoptotic regulation, chemoresistance mechanisms, and interactions with non-leukemic cells such as MSCs and Treg cells. Additionally, we explore clinical implications, including prognosis, correlation with WBC count, blast count in the bone marrow and peripheral blood, as well as its association with FLT3-ITD, NPM1 mutations, and FAB classification. Finally, this paper extensively discusses drugs that specifically target the CXCL12-CXCR4 axis, including plerixafor/AMD3100, ulocuplumab, peptide E5, and motixafortide, shedding light on their potential therapeutic value in the treatment of AML.

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作为急性髓性白血病治疗靶点的 CXCR4

对 CXCL12-CXCR4 轴在急性髓性白血病（AML）中的作用进行了广泛研究，并将针对该轴的新型抗白血病药物纳入治疗策略。然而，尽管取得了这些进展，但目前仍缺乏一篇全面、最新的综述，探讨 CXCL12-CXCR4 轴在急性髓性白血病致癌过程中的作用。在这篇综述中，我们研究了影响癌症进展的分子方面，如其对自主增殖、凋亡调控、化疗抵抗机制的影响，以及与间充质干细胞和 Treg 细胞等非白血病细胞的相互作用。此外，我们还探讨了临床意义，包括预后、与白细胞计数的相关性、骨髓和外周血中的胚泡计数，以及与 FLT3-ITD、NPM1 突变和 FAB 分类的关联。最后，本文广泛讨论了专门针对 CXCL12-CXCR4 轴的药物，包括 plerixafor/AMD3100、ulocuplumab、肽 E5 和 motixafortide，揭示了它们在治疗急性髓细胞性白血病中的潜在治疗价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Leukemia 医学-血液学

CiteScore

18.10

自引率

3.50%

发文量

270

审稿时长

3-6 weeks

期刊介绍： Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues