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

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Lucena-Araujo, Antonio R. ^{[1, 2, 3]} ; Coelho-Silva, Juan L. ^{[1, 2, 3]} ; Pereira-Martins, Diego A. ^{[1, 2, 3]} ; Silveira, Douglas R. ^[4] ; Koury, Luisa C. ^[2] ; Melo, Raul A. M. ^[5] ; Bittencourt, Rosane ^[6] ; Pagnano, Katia ^[7] ; Pasquini, Ricardo ^[8] ; Nunes, Elenaide C. ^[8] ; Fagundes, Evandro M. ^[9] ; Gloria, Ana B. ^[9] ; Kerbauy, Fabio ^[10] ; Chauffaille, Maria de Lourdes ^[10] ; Bendit, Israel ^[4] ; Rocha, Vanderson ^{[3, 4, 11]} ; Keating, Armand ^[12] ; Tallman, Martin S. ^[13] ; Ribeiro, Raul C. ^[14] ; Dillon, Richard ^[15] ; Ganser, Arnold ^[16] ; Lowenberg, Bob ^[17] ; Valk, P. J. M. ^[17] ; Lo-Coco, Francesco ^{[18, 19]} ; Sanz, Miguel A. ^{[20, 21]} ; Berliner, Nancy ^[22] ; Rego, Eduardo M. ^{[2, 3, 4]}

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^[1] Univ Fed Pernambuco, Dept Genet, Recife, PE - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Internal Med, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Ctr Cell Based Therapy, Ribeirao Preto - Brazil

^[4] Univ Sao Paulo, Fac Med, Div Hematol, Sao Paulo - Brazil

^[5] Univ Pernambuco, Dept Internal Med, Recife, PE - Brazil

^[6] Univ Fed Rio Grande do Sul, Div Hematol, Porto Alegre, RS - Brazil

^[7] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil

^[8] Univ Fed Parana, Div Hematol, Curitiba, Parana - Brazil

^[9] Univ Fed Minas Gerais, Div Hematol, Belo Horizonte, MG - Brazil

^[10] Univ Fed Sao Paulo, Dept Hematol, Sao Paulo - Brazil

^[11] Univ Oxford, Churchill Hosp, Dept Haematol, Oxford - England

^[12] Princess Margaret Canc Ctr, Toronto, ON - Canada

^[13] Mem Sloan Kettering Canc Ctr, Leukemia Serv, 1275 York Ave, New York, NY 10021 - USA

^[14] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 - USA

^[15] Kings Coll London, Fac Life Sci & Med, Dept Med & Mol Genet, London - England

^[16] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover - Germany

^[17] Erasmus MC, Dept Hematol, Rotterdam - Netherlands

^[18] Univ Tor Vergata, Dept Biopathol, Rome - Italy

^[19] Santa Lucia Fdn, Unit Neurooncohematol, Rome - Italy

^[20] Univ Valencia, Sch Med, Dept Hematol, Valencia - Spain

^[21] Inst Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Madrid - Spain

^[22] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 - USA

• Tipo de documento: Artigo Científico
• Fonte: Blood; v. 132, n. 12, p. 951-959, SEP 19 2019.
• Citações Web of Science: 1

Resumo

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 Delta Np73/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 = .004), overall survival (P < .001), cumulative incidence of relapse (P = .028), disease-free survival (P = .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. (AU)

• Processo FAPESP: 98/14247-6 - Center for Research on Cell-Based Therapy
• Beneficiário: Marco Antonio Zago
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs