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

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