PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia

Yamamoto, Tomoko; Isomura, Mariko; Xu, Yinyan; Liang, Juan; Yagasaki, Hiroshi; Kamachi, Yoshiro; Kudo, Kazuko; Kiyoi, Hitoshi; Naoe, Tomoki; Kojma, Seiji

doi:10.1016/j.leukres.2006.02.004

« Previous Next »Leukemia Research
Volume 30, Issue 9 , Pages 1085-1089, September 2006

PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia

Tomoko Yamamoto
- Departments of Pediatrics Nagoya University Graduate School of Medicine, Nagoya, Japan
- Corresponding author at: Department of Pediatrics, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. Tel.: +81 52 744 2294; fax: +81 52 744 2974.
Mariko Isomura
- Departments of Pediatrics Nagoya University Graduate School of Medicine, Nagoya, Japan
Yinyan Xu
- Departments of Pediatrics Nagoya University Graduate School of Medicine, Nagoya, Japan
Juan Liang
- Departments of Pediatrics Nagoya University Graduate School of Medicine, Nagoya, Japan
Hiroshi Yagasaki
- Departments of Pediatrics Nagoya University Graduate School of Medicine, Nagoya, Japan
Yoshiro Kamachi
- Departments of Pediatrics Nagoya University Graduate School of Medicine, Nagoya, Japan
Kazuko Kudo
- Departments of Pediatrics Nagoya University Graduate School of Medicine, Nagoya, Japan
Hitoshi Kiyoi
- Departments of Infectious Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan
Tomoki Naoe
- Departments of Hematology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Seiji Kojma
- Departments of Pediatrics Nagoya University Graduate School of Medicine, Nagoya, Japan

Received 7 July 2005; received in revised form 31 January 2006; accepted 2 February 2006. published online 07 March 2011.

Abstract

PTPN11, the gene which encodes protein tyrosine phosphatase SHP-2, plays an important role in regulating intracellular signaling. Germline mutations in PTPN11 were first observed in Noonan syndrome, while somatic mutations were identified in hematological myeloid malignancies. Recently, PTPN11 mutations have been reported in children with acute lymphoblastic leukemia (ALL). In the present study, we investigated the prevalence of mutations in PTPN11, RAS and FLT3 in samples from 95 Japanese children with ALL. We observed exon 3 and 8 missense mutations of PTPN11 in 6 children with B precursor ALL. One patient with Down syndrome and ALL had PTPN11 mutation. We also identified RAS mutations in ten patients and FLT3 internal tandem duplication (FLT3/ITD) in one patient. None of the patients had simultaneous mutations in PTPN11 and RAS, while one patient had both PTPN11 and FLT3 mutations. These data suggest that PTPN11 mutation may play an important role for leukemogenesis in a proportion of children with ALL, particularly B precursor ALL.