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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
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:
It is part of: Blood Cancer Journal, 2020, vol. 10, num. 4
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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