13q14 Deletion and Its Effect on Prognosis of Chronic Lymphocytic Leukemia

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.

MicroRNAs: Potential prognostic and theranostic biomarkers in chronic lymphocytic leukemia

“…In this study, Croce et al. evidenced that the 13q14 locus, which is eliminated in many patients with CLL, is actually the site of miR‐15a and miR‐16‐1 [45, 46]. After that, other studies also identified miR‐15a and miR‐16‐1 as tumor suppressors that were deleted or downregulated due to 13q deletion.…”

“…Furthermore, deletions of 11q, 13q, 17p, 8p, and trisomy 12 are the most common chromosomal abnormalities in CLL [43,44]. For example, cytogenetic studies have shown that 13q deletion is observed in 50% of patients with aggressive and indolent CLL [43,45]. Interestingly, the first attention to the role of miRNAs in cancers began with a study of the 13q14 region in CLL patients.…”

“…Del (13q) is the most common genetic variation at the diagnostic level of CLL and occurs in about 35%-45% of patients. Compared to del (11q), del (17p), and trisomy 12, del (13q) leads to a good prognosis [45,112]. Moreover, del (17p), mainly in the 17p13.1 region, is observed in 3%-7% of CLL cases [113,114] and causes the loss of the TP53 gene.…”

Combined Delivery of miR-15/16 through Humanized Ferritin Nanocages for the Treatment of Chronic Lymphocytic Leukemia

“…In Chronic Lymphocytic Leukemia (CLL), the deletion of the 13q14 chromosome segment is the most prevalent chromosomal aberration, affecting 50–60% of patients [ 7 ]. The importance of this deletion is further highlighted by numerous studies focusing on the microRNA miR-15a and miR-16-1 cluster, which is located within the 13q14 region.…”

“…An illustrative example of this phenomenon is the Mir-15/16 family of microRNAs. A significant reduction in the expression levels of miR-15a and miR-16-1 due to the deletion of chromosome 13q14, which commonly occurs in chronic lymphocytic leukemia (CLL) patients, was initially observed by Calin et al [ 6 , 7 ]. Significant progress has been made in elucidating the involvement of miR-15/16 in regulating the expression of various genes associated with cell proliferation, apoptosis, and the cell cycle in normal B cells, conferring to them a pivotal role of regulators of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein [ 8 ].…”