Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111, Szczecin, Poland.
Department of Anatomy and Histology, Collegium Medicum, University of Zielona Góra, Zyty 28, 65-046, Zielona Góra, Poland.
Leukemia. 2024 Nov;38(11):2303-2317. doi: 10.1038/s41375-024-02326-3. Epub 2024 Sep 11.
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 T 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.
对 CXCL12-CXCR4 轴在急性髓系白血病 (AML) 中的广泛研究导致了将针对该轴的新型抗白血病药物纳入治疗策略中。然而，尽管取得了这些进展，但缺乏全面且最新的综述来解决 CXCL12-CXCR4 轴在 AML 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，例如其对自主增殖、凋亡调节、化学抗性机制以及与间充质干细胞和 T 细胞等非白血病细胞相互作用的影响。此外，我们还探讨了临床意义，包括预后、与白细胞计数、骨髓和外周血中的原始细胞计数的相关性，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，阐明了它们在 AML 治疗中的潜在治疗价值。
