Korean J Hematol.  2010 Mar;45(1):36-45. 10.5045/kjh.2010.45.1.36.

Prognostic significance of nucleophosmin mutations and FLT3 internal tandem duplication in adult patients with cytogenetically normal acute myeloid leukemia

Affiliations
  • 1Department of Hematology/Oncology, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Korea.
  • 2Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Korea.
  • 3Department of Hematology/Oncology, Korea University Anam Hospital, Seoul, Korea.
  • 4Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea.

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.

Keyword

NPM1; FLT3-ITD; Acute myeloid leukemia; Normal karyotype
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