A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics.
Adolescent
Adult
Biomarkers, Tumor
/ genetics
Cohort Studies
Female
Fusion Proteins, bcr-abl
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Mutation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ classification
Prognosis
Sequence Analysis, RNA
/ methods
Survival Rate
Young Adult
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
20
12
2019
accepted:
01
04
2020
revised:
23
03
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
2
12
2020
Statut:
epublish
Résumé
BCR-ABL1-like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1-like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a BCR-ABL1-like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to BCR-ABL1-like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, CRLF2 overexpression and IKZF1/CDKN2A/B deletions were analyzed. Twenty out of 79 patients (12-84 years) were classified as BCR-ABL1-like (25%) based on heatmap clustering, with significant overexpression of ENAM, IGJ, and CRLF2 (P ≤ 0.001). The BCR-ABL1-like subgroup accounted for 29% of 15-60-year-old patients, with the following molecular characteristics: CRLF2 overexpression (75% of cases), IKZF1 deletions (64%), CDKN2A/B deletions (57%), and JAK2 mutations (57%). Among patients with postinduction negative minimal residual disease, those with the BCR-ABL1-like ALL signature had a higher rate of relapse and lower complete response duration than non-BCR-ABL1-like patients (P = 0.007). Thus, we have identified a new molecular signature of BCR-ABL1-like ALL that correlates with adverse prognosis in adult patients with ALL.
Identifiants
pubmed: 32332702
doi: 10.1038/s41408-020-0308-3
pii: 10.1038/s41408-020-0308-3
pmc: PMC7182567
doi:
Substances chimiques
Biomarkers, Tumor
0
Fusion Proteins, bcr-abl
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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