High FLT3 Transcript Level Is Associated with Unfavorable Prognosis in Pediatric Non-Promyelocytic Acute Myeloid Leukemia.

FLT3 is a receptor tyrosine kinase involved in the survival of hematopoietic stem cells, and mutations of FLT3 have been reported to be a risk factor in acute myeloid leukemia (AML), especially for pediatric patients. Recently, FLT3 expression level is proposed to have a prognostic significance in adults, but little is known for childhood AML.

FLT3 transcript levels at diagnosis were measured with real time quantitative reverse transcription polymerase chain reaction to verify the clinical significance in pediatric AML. FLT3 transcript levels were analyzed in 20 (M: 12, F: 8) pediatric patients with median 6 (0 – 16) years old received same treatment scheme (Leuk Res. 29; 617). Patients with secondary AML or RAEB-t were included, but patients with FAB M3 type were excluded. Relative gene expression levels were calculated by using standard curves made with KG-1 cell line copy and adjusted on the basis of the expression level of the GAPDH gene (10⁶ copy). Each gene expression level was examined in triplicate, and the mean value was subjected to analysis. The copy number of FLT3 in each sample was calculated by comparing the Ct values of samples with standard curves. Mann-Whitney test was applied for comparison of means. For survival data, Kaplan-Meier life tables were constructed and the curves were compared by means of log-rank test.

The median value of adjusted FLT copy number was 58 (0.06–19,302) x 10³. FLT3 copy number was not associated with gender, age and other risk factor except FLT3 internal tandem duplication (FLT3/ITD) which was present in 3 patients with significantly higher mean copy number (7,130 x 10³) than others (372 x 10³) (P = 0.023). The mean value of FLT3 copy number of 12 refractory or relapsed patients (2,278 x 10³) was higher than that of patients in continuous remission (48 x 10³), significantly (P = 0.031). The overall survival rate of 10 patients with high FLT3 copy number more than 50 x 10³ (25.0%) was lower than that of others (59.3%) significantly (P = 0.0457). All patients with high copy number were refractory to induction or relapsed early before post remission transplantation except 2 patients (one received bone marrow transplant from matched sibling and another received autologous peripheral stem cell transplant).

High FLT3 transcript level was an unfavorable prognostic factor for early relapse and overall survival in pediatric AML and associated with FLT3/ITD. New therapeutic scheme such as stem cell transplantation with more intensive conditioning just after complete remission and administration of FLT3 inhibitor could be applied in pediatric non-promyelocytic AML patients with high FLT3 transcript level.