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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy

Texto completo
Autor(es):
Benites, B. D. [1] ; Fattori, A. [1] ; Hackel, C. [1] ; Lorand-Metze, I. [1] ; De Souza, C. A. [1] ; Schulz, E. [1] ; Costa, F. F. [1] ; Saad, S. T. O. [2]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Dept Med Interna, Fac Med, Campinas, SP - Brazil
[2] Univ Estadual Campinas, Hemoctr, BR-13083970 Campinas, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Brazilian Journal of Medical and Biological Research; v. 41, n. 7, p. 571-578, JUL 2008.
Citações Web of Science: 4
Resumo

Apoptotic protease activating factor 1 (APAF-1) has a critical role in the regulation of apoptosis. In the present study, the mRNA expression analysis of different APAF-1 transcripts (APAF-1S, APAF-1LC, APAF-1LN, and APAF-1XL) was analyzed in bone marrow samples from 37 patients with acute myeloid leukemia (newly diagnosed, with no previous treatment). APAF-1XL and APAF-1LN transcripts (with and without an extra WD-40 repeat region, respectively) were detected in all samples, although the major form expressed was APAF-1XL in 65% of the samples (group 1), while 35% of the samples expressed primarily APAF-1LN (group 2). Only 46% of the patients presented complete remission in response to remission induction therapy (represented by less than 5% marrow blasts and hematological recovery), all but 2 cases being from group 1, 21.6% did not attain complete remission (only 1 case from group 1), and 32.4% of the patients died early. Lower expression of APAF-1XL (APAF-1XL/APAF1LN ratio < 1.2) was associated with a poor response to therapy (P = 0.0005, Fisher exact test). Both groups showed similar characteristics regarding white blood cell counts, cytogenetic data or presence of gene rearrangements associated with good prognosis as AML1-ETO, CBFB-MYH11 and PML/RARA. Since it has been shown that only the isoforms with the extra WD-40 repeat region activate procaspase-9, we suggest that low procaspase-9 activation may also be involved in the deregulation of apoptosis and chemotherapy resistance in acute myeloid leukemia. (AU)

Processo FAPESP: 05/51681-1 - Investigação funcional e caracterização do envolvimento de novos genes alvo e novas terapêuticas nas síndromes mielodisplásicas e em linhagens leucêmicas
Beneficiário:Sara Teresinha Olalla Saad
Linha de fomento: Auxílio à Pesquisa - Temático