Prognostic signature and clonality pattern of recurrently mutated genes in inactive chronic lymphocytic leukemia

Blood Cancer Journal
A M HurtadoA Jerez

Abstract

An increasing numbers of patients are being diagnosed with asymptomatic early-stage chronic lymphocytic leukemia (CLL), with no treatment indication at baseline. We applied a high-throughput deep-targeted analysis, especially designed for covering widely TP53 and ATM genes, in 180 patients with inactive disease at diagnosis, to test the independent prognostic value of CLL somatic recurrent mutations. We found that 40/180 patients harbored at least one acquired variant with ATM (n=17, 9.4%), NOTCH1 (n=14, 7.7%), TP53 (n=14, 7.7%) and SF3B1 (n=10, 5.5%) as most prevalent mutated genes. Harboring one 'sub-Sanger' TP53 mutation granted an independent 3.5-fold increase of probability of needing treatment. Those patients with a double-hit ATM lesion (mutation+11q deletion) had the shorter median time to first treatment (17 months). We found that a genomic variable: TP53 mutations, most of them under the sensitivity of conventional techniques; a cell phenotypic factor: CD38-positive expression; and a classical marker as β2-microglobulin, remained as the unique independent predictors of outcome. The high-throughput determination of TP53 status, particularly in this set of patients frequently lacking high-risk chromosomal aberrations, e...Continue Reading

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Citations

Jan 19, 2019·Oncology Letters·Kamil WdowiakJerzy Wojnar
Jan 11, 2016·Current Hematologic Malignancy Reports·Christopher Chen, Soham Puvvada
Sep 28, 2018·Cancer & Metabolism·Jack MottahedehAndrew S Goldstein
Oct 31, 2015·Blood·Thorsten Zenz, Wolfgang Huber

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Methods Mentioned

BETA
flow cytometry
PCR

Software Mentioned

MiSeq
ImMunoGeneTics
IlluminaonJboard Real Time Analysis ( RTA
MiSeq Reporter
Integrated Genome Viewer

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