Abstract

Chronic lymphocytic leukemia (CLL) is the most common leukemia affecting adults. CLL results due to uncontrolled accumulation of B lymphocytes in the body with the clinical spectrum ranging from comparatively benign disease to an aggressive form. The disease pathogenesis lies in molecular genetics, the most common alteration being the deletion in the long arm of chromosome 13, at position 14 (13q14) region. This deletion leads to the loss of important microRNAs which are involved in maintaining the critical balance of the apoptosis mechanism of cell death of B lymphocytes. As such, the imbalance contributes towards B cells' immortality and, thus, CLL arises. This significant 13q14 deletion contributes to CLL's pathogenesis and paves the way for CLL treatment, hence affecting the prognosis of the affected patients.Furthermore, the size of deletion of the long arm of chromosome 13 (13q) has a remarkable effect on its prognosis and therapeutic intervention. The minimal deleted region (MDR)/small deletion or long 13q loss/mutation, and biallelic 13q deletion or monoallelic 13q deletion are commonly seen. 13q14 deletion is an initiating defect targeting tumor suppressor gene locus deleted in lymphocytic leukemia 2 (DLEU2))/microRNA15A (MIR15A)/microRNA 16-1 (MIR 16-1). Regarding CLL treatment, conventional therapy with alkylating agents has been used for a long time, which reported low- to non-existent complete remission rates and adverse events after prolonged use. Moreover, research into the 13q14 deletion has also provided new insights into the molecular genetics and pathways that interact in such a way, making it possible to transform healthy cells into malignant cells in an entirely new fashion with a complete disregard to its original form, resulting in CLL.

Highlights

  • BackgroundChronic lymphocytic leukemia (CLL) is a tumor of B lymphocytes

  • It is characterized by the uncontrolled accumulation of B lymphocytes in the body, which usually results from apoptosis disruption [1]

  • Research has proven that 50-60% of CLL patients have the 13q14 deletion and it remains to be the most common genetic alteration which affects CLL, and this is supported by the fact that the deleted region codes for microRNAs miR15A and microRNA16A, which have an inhibitory effect on regulators of apoptosis [4,5]

Read more

Summary

Introduction

Chronic lymphocytic leukemia (CLL) is a tumor of B lymphocytes. It is characterized by the uncontrolled accumulation of B lymphocytes in the body, which usually results from apoptosis disruption [1]. As detected by FISH, the most common chromosomal abnormality associated with CLL is the deletion of 13q14, constituting approximately 50% of all cases It generally has a good prognosis but some forms have led to unfavorable outcomes. In the CLL8 trial, the combination of cyclophosphamide and rituximab reported good results in CLL patients, with mutated immunoglobulin variable heavy chain, deletion of 13q, trisomy 12, or deletion of 11q They achieved durable remission and a good survival rate following treatment with fludarabine, cyclophosphamide, and rituximab [13]. Combination therapy of lenalidomide, rituximab, and fludarabine was initially considered in untreated CLL patients, but the trial has closed prematurely due to the high toxicity and low response rate [13]

Conclusions
Disclosures
Findings
13. Hallek M: Chronic lymphocytic leukemia
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call