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

• DOI: 10.1038/bcj.2015.65
• Publication Date: 2015-08-28T13:21:59Z
• Authors: A M Hurtado; T-H Chen-Liang; B Przychodzen; C Hamedi; J Muñoz-Ballester; B Dienes; M D García-Malo; A I Antón; F de Arriba; R Teruel-Montoya; F J Ortuño; V Vicente; J P Maciejewski; A Jerez
• Keywords: Signature (topology); Hematology; Gene signature

Abstract An increasing numbers of patients are being diagnosed with asymptomatic early-stage chronic lymphocytic leukemia (CLL), no treatment indication at baseline. We applied a high-throughput deep-targeted analysis, especially designed for covering widely TP53 and ATM genes, in 180 inactive disease diagnosis, to test the independent prognostic value CLL somatic recurrent mutations. found that 40/180 harbored least one acquired variant ( n =17, 9.4%), NOTCH1 =14, 7.7%), 7.7%) SF3B1 =10, 5.5%) as most prevalent mutated genes. Harboring ‘sub-Sanger’ mutation granted an 3.5-fold increase probability needing treatment. Those double-hit lesion (mutation+11q deletion) had shorter median time first (17 months). genomic variable: mutations, them under sensitivity conventional techniques; cell phenotypic factor: CD38-positive expression; classical marker β2-microglobulin, remained unique predictors outcome. The determination status, particularly this set frequently lacking high-risk chromosomal aberrations, emerges key step, not only prediction modeling, but also exploring mutation-specific therapeutic approaches minimal residual monitoring.