[Flt-3/ITD mutation in pediatric leukemia and its clinical significance].
OBJECTIVE
Flt-3 internal tandem duplication (Flt-3/ITD) in transmembrane region is the most frequently identified mutation in Flt-3 gene, which is the most frequently happened in acute myeloid leukemia (AML) and correlated to prognosis. This study was to explore the correlation of Flt-3/ITD mutation to the occurrence of pediatric leukemia, and analyze its clinical significance.


METHODS
Flt-3/ITD mutation status in bone marrow samples from 302 children with leukemia, including 122 cases of AML, 124 cases of acute lymphoblastic leukemia (ALL), 17 cases of juvenile chronic myelogenous leukemia (JCML), and 39 cases of myelodysplastic syndromes (MDS), were examined by polymerase chain reaction (PCR) and sequencing.


RESULTS
Of the 122 AML patients, 98 (80.32%) had Flt-3 gene products in bone marrow. Flt-3/ITD mutation was detected in 21 (17.21%) of the 122 patients; the mutation rates were 42.86% (3/7) in M0, 22.22% (2/9) in M1, 12.90% (4/31) in M2, 44.44% (8/18) in M4, and 15.38% (4/26) in M5. Of the 124 ALL patients, 72 (58.06%) had Flt-3 gene products in bone marrow. Flt-3/ITD mutation was found in 2 (1.61%) of the 72 patients. DNA sequencing and Blast alignment revealed that ITD within exon 11 existed in all samples, with various duplication regions and lengths (24-95 bp). No Flt-3/ITD mutation was found in MDS patients and JCML patients. Of the 19 AML patients with Flt3/ITD mutation, the median survival time was 13.5 months (0-47 months), which was significantly shorter than that of the patients without Flt-3/ITD mutation (P<0.05). The percentage of neutrophils in peripheral blood was similar in Flt-3/ITD-positive and Flt-3/ITD-negative patients (P>0.05). Chromosome karyotype analysis showed chromosome abnormity, including t(11; 12)(p15; q13), inv16(q21; q23), and t(6; 9)(p23; q23), in 3 AML patients with Flt-3/ITD.


CONCLUSIONS
Flt-3/ITD mutations are usually detected in AML, seldom in ALL, not in MDS and JCML. Flt-3/ITD mutation is correlated to AML onset and progress. Flt-3/ITD is a significant marker to analyze AML prognosis.
Wang
Jie
J
Department of Biochemistry and Molecular Biology, Shenyang Medical College, Shenyang, Liaoning, 110034, P. R. China. wangjie19932002@163.com
Wang
Tong
T
Li
Shu
S
Lin
Li
L
Gang
Yan
Y
D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D020080:Tandem Repeat Sequences / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3