Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy
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 l...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2008-07-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2008000700004 |
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| author | B.D. Benites A. Fattori C. Hackel I. Lorand-Metze C.A. De Souza E. Schulz F.F. Costa S.T.O. Saad |
| author_facet | B.D. Benites A. Fattori C. Hackel I. Lorand-Metze C.A. De Souza E. Schulz F.F. Costa S.T.O. Saad |
| author_sort | B.D. Benites |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T01:00:36Z |
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| id | doaj.art-ad406c2c19d94e959fbd2fa6b7b02714 |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-12-13T01:00:36Z |
| publishDate | 2008-07-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-ad406c2c19d94e959fbd2fa6b7b027142022-12-22T00:04:41ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2008-07-01417571578Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapyB.D. BenitesA. FattoriC. HackelI. Lorand-MetzeC.A. De SouzaE. SchulzF.F. CostaS.T.O. SaadApoptotic 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2008000700004APAF-1Acute myeloid leukemiaApoptosisChemotherapy resistance |
| spellingShingle | B.D. Benites A. Fattori C. Hackel I. Lorand-Metze C.A. De Souza E. Schulz F.F. Costa S.T.O. Saad Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy Brazilian Journal of Medical and Biological Research APAF-1 Acute myeloid leukemia Apoptosis Chemotherapy resistance |
| title | 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_short | 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 |
| topic | APAF-1 Acute myeloid leukemia Apoptosis Chemotherapy resistance |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2008000700004 |
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