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Sci Rep ; 10(1): 5486, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32218491

RESUMO

Anthracyclines used in the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase II (topo II) isoforms, topo II α and topo IIß. In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determined expression of topo IIα and topo IIß by RT-PCR and its relationship to immunophenotype (IP) and outcomes. Treatment outcomes were analyzed by logistic or Cox regression. In 211 patients, available for analysis, topo IIα expression was significantly lower than topo IIß (P < 0.0001). In contrast to topo IIα, topo IIß was significantly associated with blast percentage in marrow or blood (P = 0.0001), CD7 (P = 0.01), CD14 (P < 0.0001) and CD54 (P < 0.0001). Event free survival was worse for CD56-negative compared to CD56-high (HR = 1.9, 95% CI [1.0-3.5], p = 0.04), and overall survival was worse for CD-15 low as compared to CD15-high (HR = 2.2, 95% CI [1.1-4.2], p = 0.02). Ingenuity pathway analysis indicated topo IIß and immunophenotype markers in a network associated with cell-to-cell signaling, hematological system development/function and inflammatory response. Topo IIß expression reflects disease biology of highly proliferative disease and distinct IP but does not appear to be an independent variable influencing outcome in adult AML patients treated with anthracycline-based therapy.


Assuntos
DNA Topoisomerases Tipo II/metabolismo , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/imunologia , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antineoplásicos/uso terapêutico , Estudos de Coortes , Citarabina/uso terapêutico , DNA Topoisomerases Tipo II/genética , Daunorrubicina/uso terapêutico , Feminino , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a Poli-ADP-Ribose/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Inibidores da Topoisomerase II/uso terapêutico , Resultado do Tratamento , Adulto Jovem
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