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

Pazhakh V, Zaker F, Alimoghaddam K, Atashrazm F - Ann Saudi Med (2011 Jan-Feb)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

ABSTRACT

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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Related in: MedlinePlus

Sequence results for NPM1 mutations. (a) Sequence result in a patient with allele A of mutant NPM1 in reverse direction; (b) sequence result in a patient with allele B of mutant NPM1 in reverse direction; (c[S1]) sequence result in a patient with allele D of mutant NPM1 in reverse direction.
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Figure 0003: Sequence results for NPM1 mutations. (a) Sequence result in a patient with allele A of mutant NPM1 in reverse direction; (b) sequence result in a patient with allele B of mutant NPM1 in reverse direction; (c[S1]) sequence result in a patient with allele D of mutant NPM1 in reverse direction.

Mentions: Among the 131 AML patients who participated in this study,23 (17.55%) patients (0.95% CI=0.107-0.244) had NPM1 mutations. The presence of these mutations was confirmed using the sequencing technique. Table 1 shows the FAB subtypes among the 23 cases with NPM1 and FLT3/ITD mutations. Among the 23 patients with NPM1 mutation, 14 (60.8%) patients had the mutant allele A, 5 (21.7%) patients had allele D, and 4 (17.4%) patients had allele B. Mutations of NPM1 were heterozygous in all 23 screened patients (Figure 3, Table 2). Of 131 patients, 21 (16.03%) patients (0.95% CI=0.092-0.229) had FLT3/ITD mutations, among whom 2 patients had M1 (9.52%); 5 patients, M2 (23.8%); 7 patients, M3 (33.33%); 1 patient, M3v (4.76%); 5 patients, M4 (23.8%); and 1 patient, M6-AML (4.76%). Among AML patients with FLT3/ITD mutations, 8 patients had mutant NPM1 (8 out of 23, 35%), while the other 13 patients had wild-type NPM1 gene (13 of 108, 12%) (Table 1).


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

Pazhakh V, Zaker F, Alimoghaddam K, Atashrazm F - Ann Saudi Med (2011 Jan-Feb)

Sequence results for NPM1 mutations. (a) Sequence result in a patient with allele A of mutant NPM1 in reverse direction; (b) sequence result in a patient with allele B of mutant NPM1 in reverse direction; (c[S1]) sequence result in a patient with allele D of mutant NPM1 in reverse direction.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3101725&req=5

Figure 0003: Sequence results for NPM1 mutations. (a) Sequence result in a patient with allele A of mutant NPM1 in reverse direction; (b) sequence result in a patient with allele B of mutant NPM1 in reverse direction; (c[S1]) sequence result in a patient with allele D of mutant NPM1 in reverse direction.
Mentions: Among the 131 AML patients who participated in this study,23 (17.55%) patients (0.95% CI=0.107-0.244) had NPM1 mutations. The presence of these mutations was confirmed using the sequencing technique. Table 1 shows the FAB subtypes among the 23 cases with NPM1 and FLT3/ITD mutations. Among the 23 patients with NPM1 mutation, 14 (60.8%) patients had the mutant allele A, 5 (21.7%) patients had allele D, and 4 (17.4%) patients had allele B. Mutations of NPM1 were heterozygous in all 23 screened patients (Figure 3, Table 2). Of 131 patients, 21 (16.03%) patients (0.95% CI=0.092-0.229) had FLT3/ITD mutations, among whom 2 patients had M1 (9.52%); 5 patients, M2 (23.8%); 7 patients, M3 (33.33%); 1 patient, M3v (4.76%); 5 patients, M4 (23.8%); and 1 patient, M6-AML (4.76%). Among AML patients with FLT3/ITD mutations, 8 patients had mutant NPM1 (8 out of 23, 35%), while the other 13 patients had wild-type NPM1 gene (13 of 108, 12%) (Table 1).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus