Lab Med Online.  2011 Jul;1(3):138-146.

Serial Determination of FLT3-ITD and NPM1 Mutations and Its Clinical Significance in Patients with MDS at Diagnosis and After Progression to AML with Myelodysplasia-related Changes

  • 1Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.


Accumulation of genetic aberrations in MDS is closely associated with progression to AML. FLT3-ITD is commonly found in AML and less frequently in MDS. FLT3-ITD in MDS is associated with a high risk of transformation to AML. Recently, significant interaction of NPM1 and FLT3-ITD was described in AML. This study was conducted to investigate the incidence and prognostic role of FLT3-ITD and NPM1 mutations (NPM1mt) on paired samples at diagnosis of MDS and AML.
Patients who were diagnosed as MDS transforming to AML were included. FLT3-ITD was detected by PCR, and NPM1mt was confirmed by direct sequencing after screening for NPM by immunohistochemistry.
AML developed in 12.0% (43/357) of MDS patients. FLT3-ITD was detected in none of MDS and 14.7% (5/34) of AML. NPM1mt was detected in 2.4% (1/41) of MDS and 11.6% (5/43) of AML. One patient with type B NPM1mt at MDS transformed to type A NPM1mt at AML. FLT3-ITD positive AML showed a tendency of shorter survival and a significantly longer time to achieve complete remission than FLT3-ITD negative AML (P=0.007). Normal karyotype AML with FLT3-ITD showed shorter overall survival than that group of AML without FLT3-ITD (P=0.017).
MDS patients acquired FLT3-ITD during AML transformation, and FLT3-ITD positive AML, especially that with normal karyotype, predicted a poor outcome. NPM1mt was identified in both MDS and AML. NPM1mt was rarely found in MDS patients, and mostly was acquired after AML transformation. Clonal evolution of NPM1mt subtype was found in one patient during acute transformation.


MDS; AML; Fms-like tyrosine kinase 3 (FLT3); Nucleophosmin (NPM)
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