Prognostic significance of nucleophosmin mutations and FLT3 internal tandem duplication in adult patients with cytogenetically normal acute myeloid leukemia.
- Author:
Yeo Kyeoung KIM
1
;
Hee Nam KIM
;
Se Ryeon LEE
;
Jae Sook AHN
;
Deok Hwan YANG
;
Je Jung LEE
;
Il Kwon LEE
;
Myung Geun SHIN
;
Hyeoung Joon KIM
Author Information
- Publication Type:Original Article
- Keywords: NPM1; FLT3-ITD; Acute myeloid leukemia; Normal karyotype
- MeSH: Adult; Bone Marrow; Cytarabine; fms-Like Tyrosine Kinase 3; Humans; Incidence; Leukemia, Myeloid, Acute; Lifting; Nuclear Proteins; Polymerase Chain Reaction; Recurrence; Stem Cell Transplantation
- From:Korean Journal of Hematology 2010;45(1):36-45
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: Nucleophosmin (NPM1) gene and fms-like tyrosine kinase 3 gene-internal tandem duplication (FLT3-ITD) mutations are the most frequent mutations in patients with cytogenetically normal (CN)-AML. We analyzed the prognostic impact of these mutations and their interactions in adults with CN-AML. METHODS: NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by GeneScan and PCR assays of bone marrow samples obtained from 121 adult patients with CN-AML (age< or =60 years at diagnosis). RESULTS: The incidence of FLT3-ITD+ was higher in the NPM1mut group than in the wild-type NPM1 gene (NPM1wt) group. The patients were divided according to their mutation status into the NPM1mut/FLT3-ITD (isolated NPM1mut), NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-, and NPM1wt/FLT3-ITD+ (isolated FLT3-ITD+) groups. The isolated NPM1mut group showed significantly better clinical outcomes in terms of relapse rate, 5-year relapse-free survival (RFS), and overall survival (OS) than the other groups. In contrast, the isolated FLT3-ITD+ group had a higher relapse rate and shorter RFS and OS than the other groups. The 5-year RFS rate was much higher among the patients who underwent allogeneic stem cell transplantation (alloSCT) than among those treated with high-dose cytarabine chemotherapy (HDAC) only as consolidation therapy in the isolated NPM1mut group and the NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD- group. 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-. Although isolated NPM1mut leads to favorable clinical outcomes of CN-AML, the role of alloSCT in such patients remains to be considered.
