Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan.
We analyzed tandem duplication in the juxtamembrane (JM) domain of the FLT3 (FMS-like tyrosine kinase 3/FLK2, CD135) gene in 94 children with acute myeloid leukemia (AML) and evaluated its correlation with clinical features. Longer polymerase chain reaction (PCR) products were observed in five patients; 1/3 of M0, 119 of M1, 1/39 of M2, 1/9 of M3 and 1/12 of M5. The sequence analyses of abnormal PCR products showed that all the abnormal products were derived from tandem duplications involving the JM domain and that all the lengthened sequences were in-frame as we previously reported. Statistical analyses revealed a significantly lower incidence of the tandem duplication in childhood AML patients than in adult patients (P < 0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P < 0.05). Our results suggest that the tandem duplication in the JM domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
T
T
Iwai
S
S
Yokota
M
M
Nakao
T
T
Okamoto
M
M
Taniwaki
N
N
Onodera
A
A
Watanabe
A
A
Kikuta
A
A
Tanaka
K
K
Asami
I
I
Sekine
H
H
Mugishima
Y
Y
Nishimura
S
S
Koizumi
Y
Y
Horikoshi
J
J
Mimaya
S
S
Ohta
K
K
Nishikawa
A
A
Iwai
T
T
Shimokawa
M
M
Nakayama
K
K
Kawakami
T
T
Gushiken
N
N
Hyakuna
T
T
Fujimoto
D000208:Acute Disease; D000328:Adult; D000595:Amino Acid Sequence; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D005091:Exons; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007438:Introns; D007951:Leukemia, Myeloid / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid; D016019:Survival Analysis; D051941:fms-Like Tyrosine Kinase 3
D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3