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Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia

BACKGROUND AND OBJECTIVES: Nucleophosmin gene mutations are frequently reported in acute myeloid leukemia (AML) patients with normal karyotype, which is also frequently associated with internal tandem duplication mutations in the FMS-like tyrosine kinase-3 gene. We sought to detect the nucleophosmin...

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Autores principales: Pazhakh, Vahid, Zaker, Farhad, Alimoghaddam, Kamran, Atashrazm, Farzaneh
Formato: Texto
Lenguaje:English
Publicado: Medknow Publications 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101725/
https://www.ncbi.nlm.nih.gov/pubmed/21245599
http://dx.doi.org/10.4103/0256-4947.75778
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author Pazhakh, Vahid
Zaker, Farhad
Alimoghaddam, Kamran
Atashrazm, Farzaneh
author_facet Pazhakh, Vahid
Zaker, Farhad
Alimoghaddam, Kamran
Atashrazm, Farzaneh
author_sort Pazhakh, Vahid
collection PubMed
description BACKGROUND AND OBJECTIVES: Nucleophosmin gene mutations are frequently reported in acute myeloid leukemia (AML) patients with normal karyotype, which is also frequently associated with internal tandem duplication mutations in the FMS-like tyrosine kinase-3 gene. We sought to detect the nucleophosmin and FMS-like tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutations among Iranian patients with AML and to assess the relationship between these mutations and the subtypes of the disease. DESIGN AND SETTING: Cross-sectional study of patients referred during 2007 through 2009. PATIENTS AND METHODS: Bone marrow and peripheral blood samples of 131 AML patients were randomly collected at the time of diagnosis and prior to treatment and the DNA extracted. After amplifying the nucleophosmin and FLT3 gene regions, positive cases were screened by conformation-sensitive gel electrophoresis and agarose gel electrophoresis techniques. RESULTS: Of 131 patients, 23 (17.5%) (0.95% CI=0.107-0.244) had nucleophosmin gene mutations. The highest frequency of such mutations was found among the subtypes of M4 (30.4%), M3 (21.7%) and M5 (17.4%). There was a high frequency of these mutations in the M3 subtype as well as a high frequency of allele D in all subtypes. Also, 21 (16.0%) samples (0.95% CI=0.092-0.229) had FLT3/ITD mutation, of which 8 samples had mutant nucleophosmin (8 of 23, 35%), and another 13 samples had wild-type nucleophosmin gene (13 of 108, 12%). There was a high degree of association between the occurrence of nucleophosmin and FLT3/ITD mutations (P=.012). CONCLUSION: Our data showed a high frequency of NPM1 mutations in the monocytic subtypes of AML, as well as a high degree of association between the occurrence of NPM1 and FLT3/ITD mutations.
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spelling pubmed-31017252011-06-16 Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia Pazhakh, Vahid Zaker, Farhad Alimoghaddam, Kamran Atashrazm, Farzaneh Ann Saudi Med Original Article BACKGROUND AND OBJECTIVES: Nucleophosmin gene mutations are frequently reported in acute myeloid leukemia (AML) patients with normal karyotype, which is also frequently associated with internal tandem duplication mutations in the FMS-like tyrosine kinase-3 gene. We sought to detect the nucleophosmin and FMS-like tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutations among Iranian patients with AML and to assess the relationship between these mutations and the subtypes of the disease. DESIGN AND SETTING: Cross-sectional study of patients referred during 2007 through 2009. PATIENTS AND METHODS: Bone marrow and peripheral blood samples of 131 AML patients were randomly collected at the time of diagnosis and prior to treatment and the DNA extracted. After amplifying the nucleophosmin and FLT3 gene regions, positive cases were screened by conformation-sensitive gel electrophoresis and agarose gel electrophoresis techniques. RESULTS: Of 131 patients, 23 (17.5%) (0.95% CI=0.107-0.244) had nucleophosmin gene mutations. The highest frequency of such mutations was found among the subtypes of M4 (30.4%), M3 (21.7%) and M5 (17.4%). There was a high frequency of these mutations in the M3 subtype as well as a high frequency of allele D in all subtypes. Also, 21 (16.0%) samples (0.95% CI=0.092-0.229) had FLT3/ITD mutation, of which 8 samples had mutant nucleophosmin (8 of 23, 35%), and another 13 samples had wild-type nucleophosmin gene (13 of 108, 12%). There was a high degree of association between the occurrence of nucleophosmin and FLT3/ITD mutations (P=.012). CONCLUSION: Our data showed a high frequency of NPM1 mutations in the monocytic subtypes of AML, as well as a high degree of association between the occurrence of NPM1 and FLT3/ITD mutations. Medknow Publications 2011 /pmc/articles/PMC3101725/ /pubmed/21245599 http://dx.doi.org/10.4103/0256-4947.75778 Text en © Annals of Saudi Medicine http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Pazhakh, Vahid
Zaker, Farhad
Alimoghaddam, Kamran
Atashrazm, Farzaneh
Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia
title Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia
title_full Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia
title_fullStr Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia
title_full_unstemmed Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia
title_short Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia
title_sort detection of nucleophosmin and fms-like tyrosine kinase-3 gene mutations in acute myeloid leukemia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101725/
https://www.ncbi.nlm.nih.gov/pubmed/21245599
http://dx.doi.org/10.4103/0256-4947.75778
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