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Molecular Oncology, Markers, Clinical Correlates |
1 Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, and2 Chang Gung University, Taoyuan, Taiwan
Purpose: We analyzed Asp835 mutations of FLT3 on paired marrow samples at diagnosis and relapse from 120 adult patients with de novo acute myeloid leukemia (AML) to determine the role of FLT3 Asp835 mutation in the relapse of AML.
Experimental Design: Asp835 mutation was analyzed by DNA PCR amplification of exon 20 of FLT3 gene followed by EcoRV digestion. All of the mutations were confirmed by sequence analysis. Mutant to wild-type allelic ratio was determined by Genescan analysis. The Expand Long Template PCR System was used to determine the allelic location of internal tandem duplication of FLT3 (FLT3/ITD) and Asp835 mutations.
Results: Thirteen patients had Asp835 mutations at diagnosis, of them 8 lost the mutations at relapse, and the remaining 5 patients carrying Asp835 mutations at diagnosis relapsed with the identical mutation types. Another 6 patients acquired Asp835 mutations at relapse. Five samples harbored both FLT3/ITD and Asp835 mutations that were found on different alleles by cloning analysis in the 3 patients studied. There were no differences in WBC count, French-American-British subtype, percentage of marrow blasts, or circulating blasts between patients with and without Asp835 mutations, whereas the difference in the prevalence of Asp835 mutations among cytogenetic/molecular subgroups was statistically significant (P = 0.025).
Conclusions: The present study showed that patients with AML had heterogeneous patterns of FLT3 Asp835 mutations, either acquisition or loss of the mutations at relapse. Asp835 mutant clone may develop as a secondary event in a subset of patients with AML.
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