High IL-7 levels in the bone marrow microenvironment mediate imatinib resistance and predict disease progression in chronic myeloid leukemia.
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.
The Key Laboratory of Hematology of Jiangxi Province, The Department of Hematology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, P.R. China.|Basic Medical school, Nanchang University, Nanchang, 330006, Jiangxi, P.R. China.|Graduate School of Medicine, Nanchang University, Nanchang, 330006, Jiangxi, P.R. China.
Xiaoyan
X
Zhang
The Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, P.R. China.
Huaijun
H
Tu
The Key Laboratory of Hematology of Jiangxi Province, The Department of Hematology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, P.R. China.|Graduate School of Medicine, Nanchang University, Nanchang, 330006, Jiangxi, P.R. China.
Yazhi
Y
Yang
The Key Laboratory of Hematology of Jiangxi Province, The Department of Hematology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, P.R. China.|Graduate School of Medicine, Nanchang University, Nanchang, 330006, Jiangxi, P.R. China.
Qian
Q
Wan
The Key Laboratory of Hematology of Jiangxi Province, The Department of Hematology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, P.R. China.|Graduate School of Medicine, Nanchang University, Nanchang, 330006, Jiangxi, P.R. China.
Lijun
L
Fang
The Key Laboratory of Hematology of Jiangxi Province, The Department of Hematology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, P.R. China.
Qiong
Q
Wu
The Key Laboratory of Hematology of Jiangxi Province, The Department of Hematology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, Jiangxi, P.R. China. thj127900@163.com.
Jian
J
Li
D017209:Apoptosis / Q000187:drug effects; D001752:Blast Crisis / Q000188:drug therapy; D001853:Bone Marrow / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology*; D015851:Interleukin-7 / Q000378:metabolism* / Q000502:physiology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
C508605:IL7 protein, human; D015851:Interleukin-7; D000068877:Imatinib Mesylate
Chronic myeloid leukemia; IL-7; Imatinib; Mesenchymal stem cells