The role of chemokine receptors in leukemia: implications for prognosis and therapeutic strategies.

In leukemia, chemokines and their receptors are central regulators of immune cell signaling and migration, profoundly influencing disease progression, cellular proliferation, differentiation, and treatment response. Receptors from the CXC and CC families play key roles in leukemia pathogenesis. In acute myeloid leukemia, CXCR1, CXCR2, and CXCR4 are associated with poor prognosis, whereas elevated levels of ligands such as CXCL8, CXCL9, and CXCL10 generally indicate better outcomes. Reduced levels of CCL5 and CCL2 are also associated with a favorable prognosis. Conversely, decreased CXCR3 expression is associated with adverse outcomes, while higher CCR7 levels correlate with more aggressive chronic lymphocytic leukemia. Chemokine signaling contributes to therapy resistance: CCL5 and CXCL8 in AML, CXCR4 in acute lymphoblastic leukemia, and elevated CXCL8 in CLL have been implicated in reduced treatment efficacy. The complex interplay between chemokines and their receptors not only drives leukemia progression but also serves as a potential biomarker for predicting therapeutic responses. Targeting these signaling pathways may offer novel approaches to overcome treatment resistance, prevent disease relapse, and improve overall patient outcomes. Understanding these mechanisms is therefore critical for developing more effective, targeted therapies against various forms of leukemia.