Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/197946
Type: Artigo de periódico
Title: Low Expression Of Apaf-1xl In Acute Myeloid Leukemia May Be Associated With The Failure Of Remission Induction Therapy.
Author: Benites, B D
Fattori, A
Hackel, C
Lorand-Metze, I
De Souza, C A
Schulz, E
Costa, F F
Saad, S T O
Abstract: 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/APAF-1LN 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.
Subject: Adult
Aged
Aged, 80 And Over
Antineoplastic Combined Chemotherapy Protocols
Apoptotic Protease-activating Factor 1
Bone Marrow Cells
Case-control Studies
Dna, Complementary
Densitometry
Female
Gene Expression Regulation, Neoplastic
Humans
Leukemia, Myeloid, Acute
Male
Middle Aged
Rna, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors
Transcription, Genetic
Treatment Failure
Tumor Markers, Biological
Young Adult
Citation: Brazilian Journal Of Medical And Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas / Sociedade Brasileira De Biofísica ... [et Al.]. v. 41, n. 7, p. 571-8, 2008-Jul.
Rights: aberto
Address: http://www.ncbi.nlm.nih.gov/pubmed/18719738
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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