[Prevalence and clinical significance of FLT3 internal tandem duplication mutation in acute leukemia].
OBJECTIVE
To evaluate the prevalence of FLT3 mutation-internal tandem duplication in acute leukemia (AL) patients and its significance.


METHODS
Genomic DNAs from 194 cases of AL were screened by polymerase chain reaction (PCR) and gel electrophoresis for FLT3-ITD mutations.


RESULTS
FLT3-ITDs were found in 37 (25.9%) of 143 de novo acute myeoloid leukemia (AML) patients, including 10/53 of M(2), 15/40 of M(3), 4/20 of M(4) and 8/23 of M(5). Significantly more FLT3 aberrations were found in AML M(3) and M(5) (P < 0.05). No FLT3-ITD was found in 25 acute lymphoid leukemia (ALL), 2 acute hybrid leukemia, 17 myelodysplastic syndromes and 7 chronic myelogenous leukemia in blast crisis. Sequence analysis of 5 cases with abnormal PCR electrophoretic patterns revealed that the ITDs were located within exon 14 from 21 bp to 60 bp, in 3 cases the ITD was a simple tandem duplication, and in 2 cases the ITD was tandem duplication with insertion, but all of the above ITD did not altered the FLT3 reading frame. FLT3-ITD was associated with a higher peripheral white cell count (P < 0.05) and a lower complete remission rate (P < 0.05), and was more prevalent in patients with normal karyotype (P < 0.05).


CONCLUSIONS
FLT3-ITD mutation occurs with a significant percentage in AML M(3) and M(5) patients. Sequences of the mutants are in frame mutation. FLT3-ITD mutation was associated with a higher peripheral white cell count and a lower complete remission rate.
Wang
Li-hong
LH
State Key Laboratory of Experimental Hematology. Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020, China.
Zhou
Chun-lin
CL
Zhang
Xin-wei
XW
Chen
Sen
S
Wang
Min
M
Wang
Jian-xiang
JX
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D020440:Gene Duplication; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020080:Tandem Repeat Sequences / Q000235:genetics*; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D051941:fms-Like Tyrosine Kinase 3