2024-03-28T11:01:37Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/109612023-10-11T11:27:40Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Sánchez, Ricardo
author
Ribera, Jordi
author
Morgades, Mireia
author
Ayala, Rosa
author
Onecha, Esther
author
Ruiz-Heredia, Yanira
author
Juárez-Rufián, Alexandra
author
de Nicolás, Rodrigo
author
Sanchez-Pina, Jose
author
Vives, Susana
author
Zamora, Lurdes
author
Mercadal, Santiago
author
Coll, Rosa
author
Cervera, Marta
author
García, Olga
author
Ribera, Josep-Maria
author
Martinez-Lopez, Joaquin
author
2020
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.
Blood Cancer J. 2020;10(4):43.
http://hdl.handle.net/20.500.12105/10961
32332702
10.1038/s41408-020-0308-3
2044-5385
Blood cancer journal
MINIMAL RESIDUAL DISEASE
HIGH-RISK
B-ALL
CLASSIFICATION
IKZF1
KINASE
A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics.