Combining gene mutation with gene expression analysis improves outcome prediction in acute promyelocytic leukemia Journal Article


Authors: Lucena-Araujo, A. R.; Coelho-Silva, J. L.; Pereira-Martins, D. A.; Silveira, D. R.; Koury, L. C.; Melo, R. A. M.; Bittencourt, R.; Pagnano, K.; Pasquini, R.; Nunes, E. C.; Fagundes, E. M.; Gloria, A. B.; Kerbauy, F.; De Lourdes Chauffaille, M.; Bendit, I.; Rocha, V.; Keating, A.; Tallman, M. S.; Ribeiro, R. C.; Dillon, R.; Ganser, A.; Löwenberg, B.; Valk, P. J. M.; Lo-Coco, F.; Sanz, M. A.; Berliner, N.; Rego, E. M.
Article Title: Combining gene mutation with gene expression analysis improves outcome prediction in acute promyelocytic leukemia
Abstract: By combining the analysis of mutations with aberrant expression of genes previously related to poorer prognosis in both acute promyelocytic leukemia (APL) and acute myeloid leukemia, we arrived at an integrative score in APL (ISAPL) and demonstrated its relationship with clinical outcomes of patients treated with all-trans retinoic acid (ATRA) in combination with anthracycline-based chemotherapy. Based on fms-like tyrosine kinase-3–internal tandem duplication mutational status; the DNp73/TAp73 expression ratio; and ID1, BAALC, ERG, and KMT2E gene expression levels, we modeled ISAPL in 159 patients (median ISAPL score, 3; range, 0-10). ISAPL modeling identified 2 distinct groups of patients, with significant differences in early mortality (P < .001), remission (P 5 .004), overall survival (P < .001), cumulative incidence of relapse (P 5 .028), disease-free survival (P 5 .03), and event-free survival (P < .001). These data were internally validated by using a bootstrap resampling procedure. At least for patients treated with ATRA and anthracycline-based chemotherapy, ISAPL modeling may identify those who need to be treated differently to maximize their chances for a cure. © 2019 by The American Society of Hematology
Journal Title: Blood
Volume: 134
Issue: 12
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2019-09-19
Start Page: 951
End Page: 959
Language: English
DOI: 10.1182/blood.2019000239
PUBMED: 31292112
PROVIDER: scopus
PMCID: PMC7484742
DOI/URL:
Notes: Article -- Export Date: 1 October 2019 -- Source: Scopus
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  1. Martin Stuart Tallman
    649 Tallman