FLT3 and NPM1 Mutations Are Uncommon in Both Low- and High-Grade Myelodysplastic Syndromes in the New Mexican Population
KE Hunt, JM Gale, MA Vasef. U. of New Mexico, Albuquerque, NM; TriCore Reference Laboratories, Albuquerque, NM
Background: The current WHO classification of hematopoietic tumors includes a provisional set of acute myeloid leukemias with gene mutations. These gene mutations are thought to contribute to the disease pathogenesis and prognosis. In the absence of cytogenetic abnormalities, FLT3-ITD mutations are associated with poor prognosis whereas NPM1 mutations (in the absence of a FLT3-ITD mutation) are associated with good prognosis. Both NPM1 and FLT3 mutations are reportedly very common in patients with acute myeloid leukemia (AML). In addition, FLT3 mutations have also been reported in rare patients with myelodysplastic syndrome (MDS). After recent introduction of anti-FLT3 targeted therapy, promising data has emerged suggesting improved outcome in patients with AML. The purpose of this study is to assess the frequency of FLT3-ITD mutations to determine if patients with high-grade MDS would benefit from anti-FLT3 therapeutic regimens.
Design: The Tricore database was searched for cases of MDS (both with and without cytogenetic abnormalities) that had a banked cell pellet. We included both low- and high-grade as well as unclassified cases of MDS. DNA was isolated and PCR was performed for the FLT3 ITD region, NPM1 insertion region along with an internal DNA quality control. Mutations are detected on capillary electrophoresis by variation in size of the PCR product.
Results: PCR amplification was successful in 27 cases. Nine of these had a cytogenetic abnormality and the other 18 were cytogenetically normal. Of the cytogenetically abnormal cases, three were high-grade (RAEB-1 or RAEB-2). Of the cytogenetically normal cases, three were also high-grade. Neither FLT3-ITD nor NPM1 mutations were detected in any of the 27 cases analyzed.
Conclusions: Although prior studies have indicated that FLT3-ITD mutations may be associated with transformation to AML, the results of our studies failed to demonstrate that these mutations play a significant role in transformation of either low-grade or high-grade cases of MDS (including those with RAEB-2). Future large scale multi-institutional studies are needed to further assess the true incidence of these mutations in MDS and their potential role in progression to AML.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 173, Tuesday Afternoon