Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Medical and Biological Research |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2008000700004 |
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/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. |
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Brazilian Journal of Medical and Biological Research |
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Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapyAPAF-1Acute myeloid leukemiaApoptosisChemotherapy resistanceApoptotic 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.Associação Brasileira de Divulgação Científica2008-07-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2008000700004Brazilian Journal of Medical and Biological Research v.41 n.7 2008reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/S0100-879X2008000700004info:eu-repo/semantics/openAccessBenites,B.D.Fattori,A.Hackel,C.Lorand-Metze,I.De Souza,C.A.Schulz,E.Costa,F.F.Saad,S.T.O.eng2008-08-14T00:00:00Zoai:scielo:S0100-879X2008000700004Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2008-08-14T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false |
dc.title.none.fl_str_mv |
Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy |
title |
Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy |
spellingShingle |
Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy Benites,B.D. APAF-1 Acute myeloid leukemia Apoptosis Chemotherapy resistance |
title_short |
Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy |
title_full |
Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy |
title_fullStr |
Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy |
title_full_unstemmed |
Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy |
title_sort |
Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy |
author |
Benites,B.D. |
author_facet |
Benites,B.D. Fattori,A. Hackel,C. Lorand-Metze,I. De Souza,C.A. Schulz,E. Costa,F.F. Saad,S.T.O. |
author_role |
author |
author2 |
Fattori,A. Hackel,C. Lorand-Metze,I. De Souza,C.A. Schulz,E. Costa,F.F. Saad,S.T.O. |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Benites,B.D. Fattori,A. Hackel,C. Lorand-Metze,I. De Souza,C.A. Schulz,E. Costa,F.F. Saad,S.T.O. |
dc.subject.por.fl_str_mv |
APAF-1 Acute myeloid leukemia Apoptosis Chemotherapy resistance |
topic |
APAF-1 Acute myeloid leukemia Apoptosis Chemotherapy resistance |
description |
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. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008-07-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2008000700004 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2008000700004 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S0100-879X2008000700004 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
dc.source.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research v.41 n.7 2008 reponame:Brazilian Journal of Medical and Biological Research instname:Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC |
instname_str |
Associação Brasileira de Divulgação Científica (ABDC) |
instacron_str |
ABDC |
institution |
ABDC |
reponame_str |
Brazilian Journal of Medical and Biological Research |
collection |
Brazilian Journal of Medical and Biological Research |
repository.name.fl_str_mv |
Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC) |
repository.mail.fl_str_mv |
bjournal@terra.com.br||bjournal@terra.com.br |
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1754302936472616960 |