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Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c-kit receptor tyrosine kinase
| Content Provider | Scilit |
|---|---|
| Author | Kitayama, H. Tsujimura, T. Matsumura, I. Oritani, K. Ikeda, H. Ishikawa, J. Okabe, M. Suzuki, M. Yamamura, K. Matsuzawa, Y. Kitamura, Y. Kanakura, Y. |
| Copyright Year | 1996 |
| Description | The c-kit proto-oncogene encodes a receptor tyrosine kinase that is crucial to hematopoiesis, melanogenesis, and gametogeneis. Although the enzymatic activity of the c-kit product (KIT) is regulated by its ligand, both the Val559-->Gly (G559) mutation in the juxtamembrane domain and the Asp814-->Val (V814) mutation in the phosphotransferase domain lead to constitutive activation of KIT. By retroviral infection of hematopoietic progenitor cells with KIT(G559) or KIT(V814), KIT(G559) induced development of granulocyte/macrophage and mast-cell colonies in vitro without the addition of exogenous growth factors. KIT(V814) induced factor-independent growth of various types of hematopoietic progenitor cells, resulting in the development of mixed erythroid/myeloid colonies in addition to granulocyte/macrophage and mast-cell colonies. Furthermore, transplantation of KIT(G559) and KIT(V814)-infected bone marrow cells led to development of acute leukemia in one of 10 and six of 10 transplanted mice, respectively. No mice developed hematologic malignancies after transplantation of wild- type KIT-infected cells. Furthermore, transgenic mice expressing KIT(V814) developed acute leukemia or malignant lymphoma. These results demonstrate a direct role of the mutant KITs, particularly KIT(V814), in tumorigenesis of hematopoietic cells and suggest that similar mutations may contribute to the development of human hematologic malignancies. |
| Related Links | https://ashpublications.org/blood/article-pdf/88/3/995/623923/995.pdf |
| DOI | 10.1182/blood.v88.3.995.995 |
| Journal | Blood |
| Issue Number | 3 |
| Volume Number | 88 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 1996-08-01 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry and Molecular Biology Research and Experimental Medicine Hematopoietic Bone Marrow Transplantation Colonies Kit Mutation V814 G559 Malignancies Cells Journal: Blood (Vol- 70, Issue- 3) |
| Content Type | Text |
| Resource Type | Article |
