1992 Fiscal Year Final Research Report Summary
Role of PDGF and TGF beta in the pathogenesis of myelofibrosis
| Project/Area Number |
03671188
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | HIROSHIMA UNIVERSITY |
|---|
Principal Investigator |
KIMURA Akiro Res.Ins.Nucl.Med.Biol.,Hirosima Univ. Associate Professor, 原爆放射能医学研究所, 助教授 (70127645)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJIMURA Kingo Res.Ins.Nucl.Med.Biol.,Hirosima Univ. Associate Professor, 原爆放射能医学研究所, 助教授 (80034114)
|
|---|
| Project Period (FY) |
1991 – 1992
|
| Keywords | Myelofibrosis / leukemia Chronic myelogeneous / growth factor Platelet derived / factor-beta Transforming growth / Bone marrow / Fibroblast |
|---|
| Research Abstract |
Platelet derived growth factor (PDGF) and transforming growth factor (TGF beta) derived from bone marrow megakaryocytes or leukemia cells have been suggested to be involved in the pathogenesis of myelofibrosis. In this project the role of these two growth factors were further studied.
Myelofibrosis frequently associated with chronic myelogenous leukemia (CML) at accelerated or blastic phase was studied in relation to PDGF. Human megakaryocytic leukemia cell line, established from a CML patient in blastic phase with myelofibrosis, was found to express mRNA for both PDGF-A chain and B chain as well as produce and secrete PDGF-AB heterodimer. In the patients with myeloid blasts and myelofibrosis in accelerated or blastic phase, both PDGF-A chain and B chain transcripts were expressed and PDGF protein was secreted from leukemia cells. On the other hand, the patients without fibrosis showed A chain transcript alone in the leukemia cells. These results suggest that expression and secretion of PDGF in the leukemia cells play an important role in the pathogenesis of myelofibrosis.
Autocrine and/or paracrine mechanism were found to operate during the proliferation of human marrow fibroblasts, a process thought to be involved in the progression of myelofibrosis. The autocrine/paracrine factor was heat unstable and acid stable peptide factor with high molecular weight (-10^6). This protein was different from PDGF, IL-1 or TNF.
|
