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Title: | A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics |
Author: | Sánchez, Ricardo Ribera, Jordi Morgades, Mireia Ayala, Rosa Onecha, Esther Ruiz Heredia, Yanira Juárez Rufián, Alexandra Nicolás, Rodrigo de Sánchez Pina, José Vives, Susana Zamora, Lurdes Mercadal, Santiago Coll, Rosa Cervera, Marta Garcia, Olga Ribera, Josep Maria Martínez López, Joaquín |
Keywords: | Leucèmia limfocítica crònica Pronòstic mèdic Chronic lymphocytic leukemia Prognosis |
Issue Date: | 24-Apr-2020 |
Publisher: | Nature Publishing Group |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41408-020-0308-3 |
It is part of: | Blood Cancer Journal, 2020, vol. 10, num. 4 |
URI: | http://hdl.handle.net/2445/173078 |
Related resource: | https://doi.org/10.1038/s41408-020-0308-3 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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SanchezR.pdf | 1.33 MB | Adobe PDF | View/Open |
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