2000 Fiscal Year Final Research Report Summary
Constitutuve activation of MAPK activity in leukemic cells-its role in cellular proliferration
| Project/Area Number |
10670966
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Saitama Prefectural University, Junior College (1999-2000)
Saitama Medical University (1998) |
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Principal Investigator |
MUROHASHI Ikuo Saitama Prefectural University, Junior College, Dep.of Med.Technology (Hematology) Professor, 教授 (90182146)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Hematological malignancies / ERK1 / ERK2 MAP kinase / Protein kinase C / PI3-kinase / Akt kinase / thalidomide / angiogenic factors / angiogenesis |
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| Research Abstract |
ERK1/ERK2 mitogen-activated protein kinase (MAPK) has been shown to play an important role in proliferation, prevention of apoptosis, and differentiation of hematopoietic cells, including malignant cell. We investigated the role and activity of MAPK activity in cells from patients with myeloid and lymphoid malignant neoplasms.
1. MAPK activity in myeloid malignancies
We showed that an appropriate hematopoietic growth factor (HG) differentially prevents apoptosis and stimulates mitosis, and stimulates the growth of leukemic cells from patients with acute myeloblastic leukemia (I Murohashi et al. : Exp Hematol 25 : 1942, 1997). AMPK activity paralleled with growth of AML blast clonogenic cells after stimulation with G-CSF or IL-3 (I Murohashi et al. : Blood 96 : 141b, 2000). AML patients could be divided into three groups by their growth patterns ; growth factor-dependent growth ; autocrine growth ; autonomous growth. Patients with spontaneous colony formation had significantly higher MAPK activity compared with those without spontaneous colony formation. It is postulated that MAPK activity must be associated with their prognosis.
2. MAPK activity in lymphoid malignancies
Constitutive MAPK activation was noted in all 100 patients with lymphoid malignancies, where phosphorylation of Akt was observed in 75% of the patients (T Takahashi, I Murohashi et al. : Blood 92 : 376a, 1998). The MAPK activity also seems to be related to their prognosis.
3. Conclusions and future studies
MAPK activity has been shown to play an important role in the growth of hematological malignancies. Further studies are required to define its effectors and functions. The role of MAPK in angiogenesis remains to be clarified.
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