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Sánchez, Ricardo; Ribera, Jordi; Morgades, Mireia; Ayala, Rosa; Onecha, Esther; Ruiz-Heredia, Yanira; Juárez-Rufián, Alexandra; de Nicolás, Rodrigo; Sánchez-Pina, José; Vives, Susana; Zamora, Lurdes; Mercadal, Santiago; Coll, Rosa; Cervera, Marta; García, Olga; Ribera, Josep-Maria; Martínez-López, Joaquín

A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics

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  • Medientyp: E-Artikel
  • Titel: A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
  • Beteiligte: Sánchez, Ricardo; Ribera, Jordi; Morgades, Mireia; Ayala, Rosa; Onecha, Esther; Ruiz-Heredia, Yanira; Juárez-Rufián, Alexandra; de Nicolás, Rodrigo; Sánchez-Pina, José; Vives, Susana; Zamora, Lurdes; Mercadal, Santiago; Coll, Rosa; Cervera, Marta; García, Olga; Ribera, Josep-Maria; Martínez-López, Joaquín
  • Erschienen: Springer Science and Business Media LLC, 2020
  • Erschienen in: Blood Cancer Journal
  • Sprache: Englisch
  • DOI: 10.1038/s41408-020-0308-3
  • ISSN: 2044-5385
  • Schlagwörter: Oncology ; Hematology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p><jats:italic>BCR-ABL1</jats:italic>-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 <jats:italic>BCR-ABL1</jats:italic>-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 <jats:italic>BCR-ABL1</jats:italic>-like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to <jats:italic>BCR-ABL1</jats:italic>-like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, <jats:italic>CRLF2</jats:italic> overexpression and <jats:italic>IKZF1</jats:italic>/<jats:italic>CDKN2A/B</jats:italic> deletions were analyzed. Twenty out of 79 patients (12–84 years) were classified as <jats:italic>BCR-ABL1</jats:italic>-like (25%) based on heatmap clustering, with significant overexpression of <jats:italic>ENAM</jats:italic>, <jats:italic>IGJ</jats:italic>, and <jats:italic>CRLF2</jats:italic> (<jats:italic>P</jats:italic> ≤ 0.001). The <jats:italic>BCR-ABL1</jats:italic>-like subgroup accounted for 29% of 15–60-year-old patients, with the following molecular characteristics: <jats:italic>CRLF2</jats:italic> overexpression (75% of cases), <jats:italic>IKZF1</jats:italic> deletions (64%), <jats:italic>CDKN2A/B</jats:italic> deletions (57%), and <jats:italic>JAK2</jats:italic> mutations (57%). Among patients with postinduction negative minimal residual disease, those with the <jats:italic>BCR-ABL1</jats:italic>-like ALL signature had a higher rate of relapse and lower complete response duration than non-<jats:italic>BCR-ABL1</jats:italic>-like patients (<jats:italic>P</jats:italic> = 0.007). Thus, we have identified a new molecular signature of <jats:italic>BCR-ABL1</jats:italic>-like ALL that correlates with adverse prognosis in adult patients with ALL.</jats:p>
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