Impact of FLT3 internal tandem duplications on Indian acute promyelocytic leukemia patients: Prognostic implications

Abstract

Despite recent advances in the treatment of acute promyelocytic leukemia (APL), early mortality and relapses still occur. With the view to evaluate the role of FLT3 mutation in APL, 54 patients (median age 28 years, range 11–57 years, male to female ratio 1.2:1, median TLC 8.4 × 10⁹/l, range 1–170 × 10⁹/l) were studied by reverse transcriptase-PCR. Forty-two patients (77%) achieved first remission (CR1). Ten (18.5%) of the 54 patients had internal tandem duplication of exons 11 and 12 of the FLT3 gene. The median TLC count was significantly higher in FLT3 positive cases (Median TLC 55.0 × 10⁹/l) as compared to FLT3 negative cases (Median TLC 6.8 × 10⁹/l) (p = 0.001). Induction CR was much lower (40%) in FLT3/ITD positive cases as compared to 86% of FLT3/ITD negative cases (p = 0.005). Early deaths too were significantly associated with FLT3/ITD positive cases (50 vs. 16% p = 0.033). The difference in the occurrence of bcrl and bcr3 isoforms was not statistically significant between the two groups. The data suggest that the presence of FLT3/ITD in APL patients confers a poor prognosis.

Keywords:

• RT-PCR
• FLT3/ITD
• PML-RARALPHA
• APL