FLT‐3 aberrations in acute promyelocytic leukaemia: clinicopathological associations and prognostic impact

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Abstract
FLT‐3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation‐loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT‐3 aberrations in a cohort of APL patients. FLT‐3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the ITD was recognized as an increase in the size of the PCR product. FLT‐3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT‐3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; ITD + D835 mutation: 1). FLT‐3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT‐3 ITD to be associated with non‐remission (P = 0·06). For disease‐free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT‐3 ITD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT‐3 inhibitors in the treatment of APL.

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