<p>The CXCR4/CXCL12 signaling axis governs leukemic stem cell dynamics within the bone marrow niche, driving migration, survival, and therapy resistance. This review examines a CXCR4-directed theranostic strategy for acute leukemia using Pentixafor and Pentixather. Pentixafor enables non-invasive visualization of CXCR4 expression, while Pentixather delivers targeted radiotherapy to CXCR4-expressing leukemic cells. We analyze how disrupting CXCR4-mediated leukemic cell-niche interactions enhances treatment efficacy and improves clinical outcomes in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). By integrating imaging and therapy, this approach offers a novel strategy to overcome microenvironment-mediated chemoresistance in hematologic malignancies. It advances personalized medicine by stratifying patients for CXCR4-targeted therapy and preserves functional hematopoietic niches, ultimately improving patient care.</p> Graphical abstract <p></p>

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CXCR4-targeted theranostics in acute leukemia: disrupting leukemic cell-microenvironment interactions with pentixafor and pentixather

  • Sana Rahimian,
  • Hossein Najafi,
  • Mohammad Doroudian

摘要

The CXCR4/CXCL12 signaling axis governs leukemic stem cell dynamics within the bone marrow niche, driving migration, survival, and therapy resistance. This review examines a CXCR4-directed theranostic strategy for acute leukemia using Pentixafor and Pentixather. Pentixafor enables non-invasive visualization of CXCR4 expression, while Pentixather delivers targeted radiotherapy to CXCR4-expressing leukemic cells. We analyze how disrupting CXCR4-mediated leukemic cell-niche interactions enhances treatment efficacy and improves clinical outcomes in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). By integrating imaging and therapy, this approach offers a novel strategy to overcome microenvironment-mediated chemoresistance in hematologic malignancies. It advances personalized medicine by stratifying patients for CXCR4-targeted therapy and preserves functional hematopoietic niches, ultimately improving patient care.

Graphical abstract