engleski

Prevalence of FLT3 Gene Internal Tandem Duplication in de novo AML/MDS

FLT3 is a receptor tyrosine kinase expressed by immature hematopoietic cells. This receptor is important for the normal development of stem cells and immune system. Mutations of FLT3 have been detected in about 30% of patients with acute myelogenous leukemia, most often involving small tandem duplications (FLT3 ITD) of amino acids within the juxtamembrane domain of the receptor. Studies suggest that mutant FLT3 cooperates with other leukemia oncogenes to confer a more aggressive phenotype. The aim of this study was to determine the prevalence of FLT3 ITD in de novo diagnosed AML/MDS patients and the association of FLT3 ITD with specific FAB subtypes and, possibly, to correlate the presence of mutation with cytogenetics. One hundred consecutive adult cases (age 22 – 78 yrs.) of de novo AML and MDS were studied. Acute promyelocytic leukemia patients were excluded. RNA obtained from leukemic samples at diagnosis was employed in RT-PCR analysis with primers according to Nakao et al. Leukemia 1996. The presence of ITD was detected as an increase in the size of the PCR product. Among all samples tested, FLT3 ITD was found in 21 cases (21%). The presence of FLT3 ITD was the highest in FAB M2 subtype (12/30 - 40%) but all 12 patients with FLT3 ITD present were negative for AML1/ETO transcript ; FLT3 ITD was found in 3 out of 13 cases of FAB M5 subtype (23%) and in none of 23 cases with MDS. These results confirm the presence of mutation only in AML, compared to MDS and the higher prevalence of mutation in patients with normal karyotype.

leukemia

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