Title | 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 |
Authors | Wang, Shu-Juan Wang, Ping-Zhang Gale, Robert Peter Qin, Ya-Zhen Liu, Yan-Rong Lai, Yue-Yun Jiang, Hao Jiang, Qian Zhang, Xiao-Hui Jiang, Bin Xu, Lan-Ping Huang, Xiao-Jun Liu, Kai-Yan Ruan, Guo-Rui |
Affiliation | Peking Univ, Peoples Hosp, Beijing, Peoples R China. Inst Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, Beijing, Peoples R China. Peking Univ, Hlth Sci Ctr, Key Lab Med Immunol, Dept Immunol,Sch Basic Med Sci,Minist Hlth,Ctr Hu, Beijing, Peoples R China. Imperial Coll London, Dept Med, Div Expt Med, Hematol Res Ctr, London, England. Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China. Peking Univ, Peoples Hosp, Beijing, Peoples R China. Liu, KY Ruan, GR (reprint author), Inst Hematol, Beijing Key Lab Hematopoiet Stem Cell Transplanta, Beijing, Peoples R China. |
Keywords | acute lymphoblastic leukemia CSRP2 prognostic factor relapse drug resistance HLA-MISMATCHED/HAPLOIDENTICAL BLOOD RESIDUAL DISEASE DETECTION POLYMERASE-CHAIN-REACTION CHRONIC MYELOID-LEUKEMIA HEPATOCELLULAR-CARCINOMA MARROW-TRANSPLANTATION CANCER PROGRAM ARRAY ANALYSIS EXPRESSION GENES |
Issue Date | 2017 |
Publisher | ONCOTARGET |
Citation | ONCOTARGET.2017,8(22),35984-36000. |
Abstract | 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. |
URI | http://hdl.handle.net/20.500.11897/473307 |
ISSN | 1949-2553 |
DOI | 10.18632/oncotarget.16416 |
Indexed | SCI(E) |
Appears in Collections: | 人民医院 |