ISSN: 1300-7777 E-ISSN: 1308-5263
Cryptochrome-1 Gene Expression is a Reliable Prognostic Indicator in Egyptian Patients with Chronic Lymphocytic Leukemia: A Cohort Prospective Study [Turk J Hematol]
Turk J Hematol. Ahead of Print: TJH-78871 | DOI: 10.4274/tjh.2017.0169  

Cryptochrome-1 Gene Expression is a Reliable Prognostic Indicator in Egyptian Patients with Chronic Lymphocytic Leukemia: A Cohort Prospective Study

Deena Mohamed Habashy, Deena Samir Eissa, Mona Mahmoud Aboelez
Department of Clinical Pathology, Hematology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Objectives Traditional prognostic factors have proven insufficient to account for the observed heterogeneity in the clinical behavior of chronic lymphocytic leukemia (CLL). Cryptochrome-1 (CRY-1) is a circadian clock gene essential in maintaining circadian rhythm and regulating cell proliferation. We evaluated CRY-1 gene expression in CLL patients, and assessed its putative role as a prognostic indicator for the clinical course of CLL. Materials and Methods Hundred CLL patients at diagnosis were studied for CRY-1 gene expression by qRT-PCR, and were followed up for assessment of time to first treatment (TFT). Results CRY-1 was expressed in 94% CLL patients at diagnosis. The median CRY-1 relative gene expression level (0.006) stratified patients into high and low expression groups. Forty of 100(40%) CLL patients showed high CRY-1, 54/100 (54%) showed low CRY-1, while 6/100 (6%) had undetectable CRY-1 gene expression. High CRY-1 gene expression was significantly associated with CD38+, Zap-70+, double CD38+Zap-70+, unfavorable/intermediate cytogenetics, unmutated IgHV gene, and diffuse marrow infiltration. Patients with highCRY-1 gene expression had shorter TFT than the low CRY-1 gene expression group. Cox-proportional hazard regression model identified CRY-1 gene expression to be independently predictive for TFT. Conclusions CRY-1 is differentially expressed among CLL patients stratifying them into low-risk and high-risk groups. CRY-1 gene expression could constitute a reliable prognostic indicator for CLL progression, complementing the role of standard well-established prognostic factors. CRY-1 gene expression could be employed as a prognostic indicator for disease progression during the initial prognostic work-up and follow-up for CLL patients.

Keywords: Chronic lymphocytic leukemia; Cryptochrome-1; Circadian genes; Time to first treatment; Prognosis; Real-time polymerase chain reaction; CD38; Zap-70




Corresponding Author: Deena Samir Eissa, Egypt


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