FLT-3 aberrations in acute promyelocytic leukaemia: clinicopathological associations and prognostic impact.
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.
Au
Wing Y
WY
Department of Medicine, Queen Mary Hospital, Hong Kong, China.
Fung
Alvin
A
Chim
Chor S
CS
Lie
Albert K
AK
Liang
Raymond
R
Ma
Edmond S K
ES
Chan
Cheuk H
CH
Wong
Kit F
KF
Kwong
Yok L
YL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012737:Sex Factors; D015996:Survival Rate; D020080:Tandem Repeat Sequences
D008565:Membrane Proteins; C084881:flt3 ligand protein