Mutation analysis of SHIP gene in acute leukemia.
- Author:
Jian-Min LUO
1
;
Ze-Lin LIU
;
Hong-Ling HAO
;
Fu-Xu WANG
;
Zuo-Ren DONG
;
Ryuzo OHNO
Author Information
1. Department of Hematology, The Second Hospital, Hebei Medical University, Shijiazhuang 050000, China.
- Publication Type:Journal Article
- MeSH:
Cell Line;
Humans;
Leukemia, Myeloid, Acute;
genetics;
Mutation;
PTEN Phosphohydrolase;
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases;
Phosphoric Monoester Hydrolases;
genetics;
physiology;
Phosphorylation;
Polymorphism, Genetic;
Precursor Cell Lymphoblastic Leukemia-Lymphoma;
genetics;
Protein-Serine-Threonine Kinases;
metabolism;
Proto-Oncogene Proteins;
metabolism;
Proto-Oncogene Proteins c-akt;
Tumor Suppressor Proteins;
physiology
- From:
Journal of Experimental Hematology
2004;12(4):420-426
- CountryChina
- Language:English
-
Abstract:
The SH2 domain containing inositol 5'-phosphatase (SHIP) was initially described as a 145 kD protein phosphorylated on tyrosines upon growth factor and cytokine stimulation. SHIP is predominately expressed in hematopoietic cells, and is a crucial negative regulator in the development of hematopoietic cells. To evaluate the role of the SHIP gene in human leukemogenesis, expression and mutation of SHIP gene in bone marrow and/or peripheral blood from 32 patients with acute myeloid leukemia (AML), 9 patients with acute lymphoblastic leukemia (ALL), as well as human hematopoietic cell lines were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), single strand conformational polymorphism (SSCP) and sequencing. The RT-PCR showed that all samples expressed SHIP gene. Mutations of SHIP gene were detected in 7 out of 32 AML patients (22%) and one out of 9 ALL patients (12%). Interestingly, two missense mutations that had been observed in one AML patient at diagnosis disappeared after complete remission (CR). In addition, Akt phosphorylation was prolonged and increased following IL-3 stimulation in this patient sample. In conclusion, data of this study demonstrate the mutation of the SHIP gene in acute leukemia for the first time and suggest a possible role of the mutation of this gene in the development of acute leukemia. SHIP serves as a tumor suppressor by negatively regulating the PI3K/Akt signaling pathway in hematopoietic cells.