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 population-based study
| Autor: | Jelena Rascon, Rimvydas Norvilas, Mindaugas Stoškus, Vaidas Dirse, Laimonas Griskevicius, Orinta Mickeviciute, Goda Vaitkeviciene, Egle Gineikiene, Ruta Semaskeviciene |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Adolescent Population Fusion Proteins bcr-abl lcsh:RC254-282 Community Health Planning JAK-STAT Fusion gene 03 medical and health sciences Young Adult 0302 clinical medicine Surgical oncology Internal medicine hemic and lymphatic diseases Genetics medicine Humans RNA-Seq Risk factor education Child education.field_of_study ABL business.industry Incidence (epidemiology) Incidence ABL-class B-ALL Infant Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Minimal residual disease 030220 oncology & carcinogenesis Child Preschool Cohort Female business 030215 immunology Research Article Signal Transduction |
| Zdroj: | BMC Cancer BMC cancer, London : BMC, 2021, vol. 21, art. no. 326, p. [1-12] BMC Cancer, Vol 21, Iss 1, Pp 1-12 (2021) |
| ISSN: | 1471-2407 |
| Popis: | 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). JAK-STAT 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. |
| Databáze: | OpenAIRE |
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