Cysteine and glycine-rich protein 2 (CSRP2) transcript levels correlate with leukemia relapse and leukemia-free survival in adults with B-cell acute lymphoblastic leukemia and normal cytogenetics
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Shu-Juan Wang1,*, Ping-Zhang Wang2,*, Robert Peter Gale3, Ya-Zhen Qin1, Yan-Rong Liu1, Yue-Yun Lai1, Hao Jiang1, Qian Jiang1, Xiao-Hui Zhang1, Bin Jiang1, Lan-Ping Xu1, Xiao-Jun Huang1,4, Kai-Yan Liu1, Guo-Rui Ruan1
1Peking University People’s Hospital and Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
2Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Medical Immunology, Ministry of Health, China, Peking University Center for Human Disease Genomics, Beijing, China
3Hematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK
4Peking-Tsinghua Center for Life Sciences, Beijing, China
*These authors contributed equally to this work
Kai-Yan Liu, email: firstname.lastname@example.org
Guo-Rui Ruan, email: email@example.com
Keywords: acute lymphoblastic leukemia, CSRP2, prognostic factor, relapse, drug resistance
Received: December 10, 2016 Accepted: March 11, 2017 Published: March 21, 2017
Relapse is the major cause of treatment-failure in adults with B-cell acute lymphoblastic leukemia (ALL) achieving complete remission after induction chemotherapy. Greater precision identifying persons likely to relapse is important. We did bio-informatics analyses of transcriptomic data to identify mRNA transcripts aberrantly-expressed in B-cell ALL. We selected 9 candidate genes for validation 7 of which proved significantly-associated with B-cell ALL. We next focused on function and clinical correlations of the cysteine and glycine-rich protein 2 (CSRP2). Quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine gene transcript levels in bone marrow samples from 236 adults with B-cell ALL compared with samples from normals. CSRP2 was over-expressed in 228 out of 236 adults (97%) with newly-diagnosed B-cell ALL. A prognostic value was assessed in 168 subjects. In subjects with normal cytogenetics those with high CSRP2 transcript levels had a higher 5-year cumulative incidence of relapse (CIR) and worse relapse-free survival (RFS) compared with subjects with low transcript levels (56% [95% confidence interval, 53, 59%] vs. 19% [18, 20%]; P = 0.011 and 41% [17, 65%] vs. 80% [66–95%]; P = 0.007). In multivariate analyses a high CSRP2 transcript level was independently-associated with CIR (HR = 5.32 [1.64–17.28]; P = 0.005) and RFS (HR = 5.56 [1.87, 16.53]; P = 0.002). Functional analyses indicated CSRP2 promoted cell proliferation, cell-cycle progression, in vitro colony formation and cell migration ability. Abnormal CSRP2 expression was associated with resistance to chemotherapy; sensitivity was restored by down-regulating CSRP2 expression.
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