FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group.

Abstract:

:Genomic DNA from 106 cases of adult de novo acute myeloid leukaemia (AML) was screened by polymerase chain reaction (PCR) and gel electrophoresis for FLT3 internal tandem duplication (ITD) mutations within the juxtamembrane (JM) domain. FLT3 mutations were detected in 14 cases (13.2%) and occurred in FAB types M1 (4 out of 14 cases), M3 (1 out of 10 cases), M4 (5 out of 37 cases) and M5 (4 out of 11 cases). Sequence analysis of four cases with abnormal PCR electrophoretic patterns revealed in frame duplications in the region of exon 11 of between 27 and 111 base pairs. Three are predicted to result in the tandem duplication of adjacent amino acid residues and one to result in a tandem duplication plus insertion of a novel amino acid motif. Statistical analysis showed the FLT3 mutations to be a strong prognostic factor, with patients lacking the mutation surviving significantly longer from diagnosis (mean 29.1 months) than those with an ITD (mean 12.8 months; P = 0.0002). Thirteen of the 14 patients with FLT3 mutations died within 18 months of diagnosis. FLT3 mutations were of prognostic significance in good risk disease (P = 0.04), as well as in patients with standard risk disease (P = 0.0096). This study demonstrates that the FLT3 ITD mutation occurs in a significant percentage of adult AML cases and is an important adverse prognostic factor that appears independent of conventional karyotypic findings.

journal_name

Br J Haematol

authors

Abu-Duhier FM,Goodeve AC,Wilson GA,Gari MA,Peake IR,Rees DC,Vandenberghe EA,Winship PR,Reilly JT

doi

10.1046/j.1365-2141.2000.02317.x

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

190-5

issue

1

eissn

0007-1048

issn

1365-2141

pii

bjh2317

journal_volume

111

pub_type

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