A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
Sánchez, Ricardo (Centro Nacional de Investigaciones Oncológicas)
Ribera Salas, Jordi (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Morgades, Mireia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ayala, Rosa (Universidad Complutense de Madrid)
Onecha, Esther (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Ruiz-Heredia, Y. (Hospital Universitario 12 de Octubre (Madrid))
Juárez-Rufián, A. (Hospital Universitario 12 de Octubre (Madrid))
de Nicolás, R. (Hospital Universitario 12 de Octubre (Madrid))
Sánchez-Pina, J. (Hospital Universitario 12 de Octubre (Madrid))
Vives Polo, Susana (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Zamora, Lurdes (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Mercadal, Santiago (Hospital Universitari de Bellvitge)
Coll, Rosa (Hospital Universitari de Girona Doctor Josep Trueta)
Cervera, Marta (Hospital Universitari Joan XXIII de Tarragona)
García, Olga (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ribera, Jose-Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Martínez-López, J. (Universidad Complutense de Madrid)
Universitat Autònoma de Barcelona

Date:	2020
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Genetics research ; Cancer genomics ; Translational research
Published in:	Blood Cancer Journal, Vol. 10 Núm. 4 (january 2020) , p. 43, ISSN 2044-5385

DOI: 10.1038/s41408-020-0308-3
PMID: 32332702

11 p, 1.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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