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Molecular Prognostic Markers and Their Clinical Relevance in Chronic Lymphocytic Leukemia


Authors: V. Navrkalová 1;  B. Kantorová 1;  M. Jarošová 2;  Š. Pospíšilová 1
Authors‘ workplace: Interní hematologická a onkologická klinika LF MU a FN Brno2 Hemato‑ onkologická klinika LF UP a FN Olomouc 1
Published in: Klin Onkol 2015; 28(Supplementum 3): 6-15
doi: https://doi.org/10.14735/amko20153S6

Overview

Chronic lymphocytic leukemia is the most common leukemia in Western countries affecting particularly elderly adults. Despite the constantly improving therapy options, chronic lymphocytic leukemia is still an incurable disease owing to considerable clinical and bio­logical heterogeneity. Pathogenesis of chronic lymphocytic leukemia is not fully understood; however, aberrant antigenic stimulation, apoptosis deregulation and microenvironmental interactions play a crucial role in disease development. The most important molecular prognostic markers with clinical relevance include mutation status of heavy‑chain immunoglobulin genes (IGHV), presence of cytogenetic aberrations and TP53 and ATM gene mutations. Recent implementation of next generation sequencing technologies has enabled more accurate analysis of both well‑established and novel potential prognostic markers. The most relevant candidates are mutations in SF3B1, NOTCH1 and BIRC3 genes, which are now intensively studied with respect to their clinical importance. The other examined molecular mechanisms of chronic lympho­cytic leukemia pathogenesis include deregulation of B‑ cell receptor signalization and abnormal regulation of gene expression by microRNA. The precise characterization of molecular abnormalities improves the risk stratification of chronic lymphocytic leukemia patients, which could possibly benefit from new treatment approaches.

Key words:
chronic lymphocytic leukemia –  biological markers –  chromosome aberations –  mutations –  prognosis

This work was supported by the grants IGA MH CZ NT13493-4/2012, NT13576-4/2012, NT13576, AZV MZ ČR No. 15-30015A-4/2015 a 15-31834A-4/2015 a TAČR TE02000058.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
30. 7. 2015

Accepted:
4. 8. 2015


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