Abstract
ObjectiveTraditional prognostic factors have proved insufficient to account for heterogeneity in the clinical behavior of chronic lymphocytic leukemia (CLL). Cryptochrome-1 (CRY-1) is a circadian clock gene essential in maintaining the circadian rhythm and regulating cell proliferation. We evaluated CRY-1 gene expression in CLL and addressed its putative role as a prognostic indicator for the clinical course of CLL.Materials and MethodsA total of 100 CLL patients at diagnosis were studied for CRY-1 gene expression by real-time reverse-transcription polymerase chain reaction and were followed for assessment of time to first treatment (TFT).Results CRY-1 was expressed in 94% of the 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, and 6/100 (6%) had undetectable CRY-1 gene expression. High CRY-1 gene expression was concordant with CD38+, Zap-70+, and double CD38+Zap-70+ expression; unfavorable/intermediate cytogenetics; unmutated immunoglobulin heavy-chain variable-region gene; and diffuse marrow infiltration. The high CRY-1 gene expression patient group exhibited shorter TFT than the patients with low CRY-1 gene expression. A Cox proportional hazard regression model identified CRY-1 gene expression to be independently predictive for TFT.Conclusion 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.
Highlights
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative neoplasm defined by proliferation and accumulation of morphologically mature, immunologically dysfunctional monoclonal B cells in the peripheral blood (PB), bone marrow (BM), and lymphatic tissues [1].The clinical course of CLL is heterogeneous and difficult to predict; some patients may exhibit rapid disease progression while others may live for decades without requiring treatment [2]
High CRY1 gene expression was concordant with CD38+, Zap-70+, and double CD38+Zap-70+ expression; unfavorable/intermediate cytogenetics; unmutated immunoglobulin heavy-chain variable-region gene; and diffuse marrow infiltration
A Cox proportional hazard regression model identified CRY1 gene expression to be independently predictive for to first treatment (TFT)
Summary
The clinical course of CLL is heterogeneous and difficult to predict; some patients may exhibit rapid disease progression while others may live for decades without requiring treatment [2]. Treatment of the latter group would risk the development of therapy-related complications that might affect the quality of life and/or survival. Traditional prognostic factors have proved insufficient to account for heterogeneity in the clinical behavior of CLL, indicating a need for further prognostic indicators that can better correlate with patients’ clinical outcome and survival [4,5]. The immunoglobulin heavy-chain variable-region (IgHV) gene mutational status correlates with clinical behavior and represents a robust prognostic indicator for CLL. IgHV gene sequencing is complicated and time-consuming for routine laboratories; exploring an alternative for IgHV gene mutations is a priority [6]
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Schedule a callMore From: Turkish journal of haematology : official journal of Turkish Society of Haematology
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