Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/10961
Título
A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics.
Autor(es)
Sánchez, Ricardo | Ribera, Jordi | Morgades, Mireia | Ayala, Rosa | Onecha, Esther | Ruiz-Heredia, Yanira | Juárez-Rufián, Alexandra | de Nicolás, Rodrigo | Sanchez-Pina, Jose | Vives, Susana | Zamora, Lurdes | Mercadal, Santiago | Coll, Rosa | Cervera, Marta | García, Olga | Ribera, Josep-Maria | Martinez-Lopez, Joaquin CNIO
Fecha de publicación
2020
Cita
Blood Cancer J. 2020;10(4):43.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
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