Title Low incidence of ABL-class and JAK-STAT signaling pathway alterations in uniformly treated pediatric and adult B-cell acute lymphoblastic leukemia patients using MRD risk-directed approach – a populationbased study /
Authors Norvilas, Rimvydas ; Dirsė, Vaidas ; Semaškevičienė, Rūta ; Mickevičiūtė, Orinta ; Gineikienė, Eglė ; Stoškus, Mindaugas ; Vaitkevičienė, Goda Elizabeta ; Rascon, Jelena ; Griškevičius, Laimonas
DOI 10.1186/s12885-020-07781-6
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Is Part of BMC cancer.. London : BMC. 2021, vol. 21, art. no. 326, p. [1-12].. eISSN 1471-2407
Keywords [eng] B-ALL ; ABL-class ; JAK-STAT ; RNA-Seq
Abstract [eng] Background: ABL-class and JAK-STAT signaling pathway activating alterations have been associated with both a poor post-induction minimal residual disease (MRD) response and an inferior outcome in B-cell acute lymphoblastic leukemia (B-ALL). However, in most of the studies patients received non-uniform treatment. Methods: We performed a population-based analysis of 160 (122 pediatric and 38 adult) Lithuanian BCR-ABL1- negative B-ALL patients who had been uniformly treated according to MRD-directed NOPHO ALL-2008 protocol. Targeted RNA sequencing and FISH analysis were performed in cases without canonical B-ALL genomic alterations (high hyperdiploids and low hypodiploids included). Results: We identified ABL-class fusions in 3/160 (1.9%) B-ALL patients, and exclusively in adults (p = 0.003). JAKSTAT pathway fusions were present in 4/160 (2.5%) cases. Of note, P2RY8-CRLF2 fusion was absent in both pediatric and adult B-ALL cases. Patients with ABL-class or JAK-STAT pathway fusions had a poor MRD response and were assigned to the higher risk groups, and had an inferior event-free survival (EFS) / overall survival (OS) compared to patients without these fusions. In a multivariate analysis, positivity for ABL-class and JAK-STAT fusions was a risk factor for worse EFS (p = 0.046) but not for OS (p = 0.278) in adults. Conclusions: We report a low overall frequency of ABL-class and JAK-STAT fusions and the absence of P2RY8-CRLF2 gene fusion in the Lithuanian BCR-ABL1 negative B-ALL cohort. Future (larger) studies are warranted to confirm an inferior event-free survival of ABL-class/JAK-STAT fusion-positive adult patients in MRD-directed protocols.
Published London : BMC
Type Journal article
Language English
Publication date 2021
CC license CC license description