TY - JOUR
T1 - Combining gene mutation with gene expression analysis improves outcome prediction in acute promyelocytic leukemia
AU - Lucena-Araujo, Antonio R.
AU - Coelho-Silva, Juan L.
AU - Pereira-Martins, Diego A.
AU - Silveira, Douglas R.
AU - Koury, Luisa C.
AU - Melo, Raul A.M.
AU - Bittencourt, Rosane
AU - Pagnano, Katia
AU - Pasquini, Ricardo
AU - Nunes, Elenaide C.
AU - Fagundes, Evandro M.
AU - Gloria, Ana B.
AU - Kerbauy, Fábio
AU - De Lourdes Chauffaille, Maria
AU - Bendit, Israel
AU - Rocha, Vanderson
AU - Keating, Armand
AU - Tallman, Martin S.
AU - Ribeiro, Raul C.
AU - Dillon, Richard
AU - Ganser, Arnold
AU - Löwenberg, Bob
AU - Valk, P. J.M.
AU - Lo-Coco, Francesco
AU - Sanz, Miguel A.
AU - Berliner, Nancy
AU - Rego, Eduardo M.
N1 - Funding Information:
This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP; grant 1998/14247-6) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant 573754/2008-0).
Funding Information:
This work was supported by Funda??o de Amparo a Pesquisa do Estado de S?o Paulo (FAPESP; grant 1998/14247-6) and Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq; grant 573754/2008-0).
Publisher Copyright:
© 2019 by The American Society of Hematology
PY - 2019/9/19
Y1 - 2019/9/19
N2 - 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.
AB - 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.
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U2 - 10.1182/blood.2019000239
DO - 10.1182/blood.2019000239
M3 - Article
C2 - 31292112
AN - SCOPUS:85072508585
SN - 0006-4971
VL - 134
SP - 951
EP - 959
JO - Blood
JF - Blood
IS - 12
ER -