High IL-7 levels in the bone marrow microenvironment mediate imatinib resistance and predict disease progression in...

Chronic myeloid leukemia (CML) is a three-stage myeloproliferative disease caused by translocation between chromosomes 9 and 22. Although tyrosine kinase inhibitors (TKI) are highly effective in the treatment of CML, numerous clinical trials have shown that many patients become refractory or drug resistance, especially those in the blastic crisis of CML. The molecular mechanisms underlying CML, however, remain poorly understood. In the present study, we used a coculture model to address possible mechanisms underlying the involvement of bone marrow microenvironment in the drug resistance of CML. Our data show that interleukin-7(IL-7) levels in the bone marrow of CML patients in blastic crisis are significantly higher than those of both healthy persons and CML patients in chronic and accelerated phases. The increased IL-7 was secreted by mesenchymal stem cells (MSC) in the bone marrow, which may protect leukemic cells from apoptosis induced by imatinib through JAK1/STAT5 signaling pathway. Our findings suggest that therapeutic strategies IL-7 signaling pathway may represent a promising approach for improving CML therapy, especially for patients in blastic crisis.