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

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.

WT1 overexpression predicted good outcomes in adult B-cell acute lymphoblastic leukemia patients receiving chemotherapy

“…MRD was quantified by analysing leukemia-associated aberrant immune phenotypes (LAIPs) with flow cytometry as previously described [24]. A positive MRD test was defined as ≥ 0.1% of the cells with an LAIP phenotype [25].…”

CSRP2 suppresses colorectal cancer progression via p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways

“…In the nucleus, CRPs can interact with transcription factors, such as MyoD, SRF, and GATA family proteins, to facilitate smooth (CRP1 and CRP2) or striated muscle (CRP3) differentiation 5 . In the cytoplasm, they decorate filamentous actin structures and participate in cytoskeletal remodeling 6 . However, the exact function of these proteins remains unclear.…”

“…It is involved in actin cytoskeleton rearrangement, and a lack of CSRP2 can promote the migration of vascular smooth muscle cells 8 . CSRP2 has been studied in several tumors, including breast 9 , gastric 10 , hepatocellular cancers 11 and lymphoblastic leukemia 6 and is involved in the proliferation, migration and invasion of tumor cells. However, the CSRP2 role is controversial in different tumors, and its precise cellular function needs to be further elucidated.…”

<p>Inhibition of CSRP2 Promotes Leukemia Cell Proliferation and Correlates with Relapse in Adults with Acute Myeloid Leukemia</p>

“…8 Our previous study suggests that CSRP2 is highly expressed in the blasts from patients with adult B cell acute lymphoblastic leukemia (B-ALL); and high expression of CSRP2 is an independent adverse prognostic factor for normal karyotype adult B-ALL. 9 To date, there is no study on the function and the prognostic relevance of CSRP2 in adult AML patients. Here, we examined the levels of CSRP2 transcripts for an association with relapse probability in adults with AML.…”