[Mutation analysis of SHIP gene in acute leukemia].
OBJECTIVE
The SH2 domain containing inositol 5'-phosphatase (SHIP) is predominately expressed in hematopoietic cells, and is a crucial negative regulator in the development of hematopoietic cells. This paper is to evaluate the role of the SHIP gene in human leukemogenesis.


METHODS
Expression of SHIP gene in bone marrow and/or peripheral blood from 32 patients with acute myeloid leukemia (AML), 9 with acute lymphoblastic leukemia (ALL), as well as human hematopoietic cell lines was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), single strand conformational polymorphism (SSCP) and DNA sequencing.


RESULTS
RT-PCR showed that all samples expressed SHIP gene. Mutations of SHIP gene were detected in 7 (22%) of 32 AML patients and one (12%) of 9 ALL patients. Interestingly, two missense mutations that had been observed in a AML patient at diagnosis disappeared after complete remission (CR). In addition, in vitro Akt phosphorylation was prolonged and increased following IL-3 stimulation of this patient's cells.


CONCLUSIONS
Our data demonstrate for the first time the mutation of SHIP gene in acute leukemia and suggest a possible role of the mutation of this gene in the development of acute leukemia. SHIP may serve as a tumor suppressor by negatively regulating the PI3K/Akt signaling pathway in hematopoietic cells.
Luo
Jian-min
JM
Department of Hematology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Liu
Ze-lin
ZL
Hao
Hong-ling
HL
Wang
Fu-xu
FX
Dong
Zuo-ren
ZR
Ryuzo
Ohno
O
D015153:Blotting, Western; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D018922:HL-60 Cells; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D007377:Interleukin-3 / Q000494:pharmacology; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D018807:Polymorphism, Single-Stranded Conformational; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells
D007377:Interleukin-3; D051058:Oncogene Protein v-akt; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases