[Expression of FLT3 internal tandem duplication in pediatric patients with acute myeloid leukemia and its correlation with multidrug resistance].
This study was aimed to investigate the expression of FLT3 internal tandem duplication (FLT3-ITD) in pediatric patients with acute myeloid leukemia (AML) and to analyse the clinical features of patients with mutations and the relation of FLT3-ITD with multidrug resistance gene 1 (mdr1). RT-PCR was used to determine the expressions of FIT3-ITD and mdr1 gene in bone marrow samples from 81 new diagnosed pediatric patients with AML, the cytogenetics and immunophenotypes of bone marrow cells were routinely examined. The results indicated that the FLT3-ITDs were detected in 8 out of 81 pediatric patients (9.88%) and all mutations detected were hybrid, while less frequently this mutation was detected in adult patients. Although they were irrelevant with sex and immunophenotypes, the mutations seemed predominant in older pediatric patients. The leukocyte counts and bone marrow blast cell counts in pediatric patients with FLT3-ITD at diagnosis were higher than those in pediatric patients without FLT3-ITD (p = 0.001 and p = 0.041 respectively), but the normal chromosomes were found in most pediatric patients with FLT-ITD. The patients with FLT3-ITD had lower induction remission rate (only 25%), but the patients without FLT3-ITD had higher remission rate (76.1%). According results detected by RT-PCR, the mdr1 gene was found in 27 pediatric patients, but only 3 out of 8 pediatric patients with FLT3-ITD were detected to express both FLT3-ITD and mdr1, which suggests unrelation between FLT3-ITD occurrence and mdr1 expression. It is concluded that the FLT3-ITD is frequent mutation in pediatric patients with AML, the prognosis is worse and the induction remission rate is lower in these patients, but the FLT3-ITD not relates with the mdr1, which suggests that the common MDR modulators may be un effective for therapy of the patients with FLT3-ITD.
Zhao
Jiang-Ning
JN
Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen 361004, China.
Qiao
Zhen-Hua
ZH
Xu
Lian-Rong
LR
Lu
Quan-Yi
QY
Niu
Xiao-Qing
XQ
Zhang
Peng
P
Wang
Zhao
Z
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D009154:Mutation; D011379:Prognosis; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3