» Articles » PMID: 38067115

Characterization of Three Somatic Mutations in the 3'UTR of and Their Inverse Correlation with Lymphocytosis in Chronic Lymphocytic Leukemia

Overview
Journal Cells
Publisher MDPI
Date 2023 Dec 9
PMID 38067115
Authors
Affiliations
Soon will be listed here.
Abstract

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B-lymphocytes in peripheral blood, bone marrow, and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly to aggressive CLL. The significant heterogeneity of CLL underscores the importance of identifying novel prognostic markers. Recently, the RAS-related gene has emerged as both a driver oncogene and a potential marker for CLL progression, with higher expression associated with poorer disease prognosis. Although missense somatic mutations in the coding sequence of have not been described in CLL, this study reports the frequent detection of three somatic mutations in the 3' untranslated region (3'UTR) affecting positions +26, +53, and +180 downstream of the stop codon in the mRNA. An inverse relationship was observed between these three somatic mutations and mRNA expression, which correlated with lower blood lymphocytosis. These findings highlight the importance of overexpression in CLL development and prognosis and point to somatic mutations in its 3'UTR as novel mechanistic clues. Our results may contribute to the development of targeted therapeutic strategies and improved risk stratification for CLL patients.

Citing Articles

Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer.

Cifuentes C, Oeste C, Fernandez-Pisonero I, Hortal A, Garcia-Macias C, Hochart J Mol Cancer. 2024; 23(1):142.

PMID: 38987766 PMC: 11234613. DOI: 10.1186/s12943-024-02054-3.

References
1.
Hortal A, Lacuna M, Cifuentes C, Alcoceba M, Bustelo X, Gonzalez M . An Optimized Single Nucleotide Polymorphism-Based Detection Method Suggests That Allelic Variants in the 3' Untranslated Region of Correlate with Treatment Response in Chronic Lymphocytic Leukemia Patients. Cancers (Basel). 2023; 15(3). PMC: 9913312. DOI: 10.3390/cancers15030644. View

2.
Wei W, Gao W, Li Q, Liu Y, Chen H, Cui Y . Comprehensive characterization of posttranscriptional impairment-related 3'-UTR mutations in 2413 whole genomes of cancer patients. NPJ Genom Med. 2022; 7(1):34. PMC: 9163142. DOI: 10.1038/s41525-022-00305-0. View

3.
Bosch F, Dalla-Favera R . Chronic lymphocytic leukaemia: from genetics to treatment. Nat Rev Clin Oncol. 2019; 16(11):684-701. DOI: 10.1038/s41571-019-0239-8. View

4.
Mayo O . A century of Hardy-Weinberg equilibrium. Twin Res Hum Genet. 2008; 11(3):249-56. DOI: 10.1375/twin.11.3.249. View

5.
Ghia P, Ferreri A, Caligaris-Cappio F . Chronic lymphocytic leukemia. Crit Rev Oncol Hematol. 2007; 64(3):234-46. DOI: 10.1016/j.critrevonc.2007.04.008. View