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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Prognostic implications of NPM1 mutations and FLT3 internal tandem duplications in Egyptian patients with cytogenetically normal acute myeloid leukemia
Hematology, Volume 19, No. 1, Year 2014
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Description
Nucleophosmin (NPM1) and fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) gene mutations represent the most frequent molecular aberrations in patients with cytogenetically normal-acute myeloid leukemia (CN-AML). We analyzed the prognostic impact of these mutations and their interactions in adults with CN-AML. NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by polymerase chain reaction and GeneScan assays of bone marrow samples obtained from newly diagnosed 104 CN-AML patients. FLT3-ITD+ and NPM1mut were detected in 36 (34.6%) and 30 (28.8%) out of 104 subjects, respectively, 16 cases (15.4%) had double NPM1mut/FLT3-ITD+. The incidence of FLT3-ITD+ was significantly higher in the NPM1mut group than in the NPM1 wild (NPM1wt) group (P = 0.018). Statistical analysis revealed that isolated NPM1mut group had a better clinical outcomes in terms of higher complete response (CR) rate (P = 0.01) and a trend towards favorable overall survival (OS) and disease-free survival (DFS) (P = 0.28, 0.40, respectively). In contrast, the isolated FLT3-ITD+ group had an unfavorable outcome in terms of lower CR rate (P = 0.12), shorter OS, and DFS (P < 0.0001 for both). The NPM1mut/FLT3-ITD-group had the best OS and DFS, while the NPM1wt/FLT3-ITD+ group had the worst OS and DFS than other groups (NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD) (P < 0.0001 for both). Multivariate Cox regression analysis showed that age and FLT3/ITD+ were independent poor prognostic factors for OS (P = 0.006, <0.0001, respectively), while FLT3/ITD+ was independent predictor for DFS (P = 0.04). However, NPM1mut did not have a significant impact on OS and DFS. In conclusion, adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-. Patients with NPM1mut/FLT3-ITD-. had the best prognosis in terms of higher CR, OS, and DFS, while those with NPM1mut/FLT3-ITD+ had the worst CR rate, and NPM1wt/FLT3-ITD+ had the lowest OS and DFS. © W. S. Maney & Son Ltd 2014.
Authors & Co-Authors
Shamaa, Sameh
Egypt, Mansoura
Faculty of Medicine
Laimon, Nabil
Egypt, Mansoura
Faculty of Medicine
Aladle, Doaa Abd Allah M.
Egypt, Mansoura
Faculty of Medicine
Azmy, Emad A.
Egypt, Mansoura
Faculty of Medicine
Elghannam, Doaa Mahmoud
Egypt, Mansoura
Faculty of Medicine
Salem, Dalia Abdel Raouf
Egypt, Mansoura
Faculty of Medicine
Taalab, Mona M.
Egypt, Mansoura
Faculty of Medicine
Statistics
Citations: 15
Authors: 7
Affiliations: 1
Identifiers
Doi:
10.1179/1607845413Y.0000000085
ISSN:
10245332
e-ISSN:
16078454
Research Areas
Cancer
Genetics And Genomics
Study Design
Cohort Study
Study Approach
Quantitative