CXCR4 as a therapeutic target in acute myeloid leukemia.

Leukemia

Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111, Szczecin, Poland.

Published: November 2024

AI Article Synopsis

  • Extensive research has focused on the CXCL12-CXCR4 axis in acute myeloid leukemia (AML), leading to the development of new anti-leukemia drugs targeting this pathway.
  • The review highlights the axis's role in cancer progression, covering its influence on growth, resistance to treatment, and interactions with other cell types like MSCs and T cells.
  • It also discusses the clinical implications of the CXCL12-CXCR4 axis, including its connections to prognosis and specific mutations, as well as examining various drugs that target this axis and their therapeutic potential in AML.

Article 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 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.

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Source
http://dx.doi.org/10.1038/s41375-024-02326-3DOI Listing

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