1994 Fiscal Year Final Research Report Summary
STUDY ON THE IDENTIFICATION OF MYELOMA PRECURSOR CELLS AND THEIR INDUCTION OF DIFFERENTIATION
| Project/Area Number |
05454332
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | HIROSIMA UNIVERSITY |
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Principal Investigator |
KAWANO Michio Hiroshima Univ., Medical Hospital, Assistant Professor, 医学部・附属病院, 講師 (40161343)
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| Co-Investigator(Kenkyū-buntansha) |
KURAMOTO Atsushi Research Institute for Radiation Biology and Medicine, Hiroshima Univ.Professor, 原爆放射能医学研究所, 教授 (50034070)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Myeloma / Immature myeloma cells / Tumor precursor / Interleukin 6 / Cell differentiation / Plasma cell / Asdhesion molecule / MPC-1 |
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| Research Abstract |
In the myelomas of well-differentiated hematological malignancies, myeloma cells are heterogeneous in the bone marrow. This heterogeneity of myeloma cells was clarified by expression of the adhesion molecules such as MPC-1 and VLA-5. Myeloma cells were classified into VLA-5^-MPC-1^- immature, VLA-5^- MPC-1^+ intermediate and VLA-5^+ MPC-1^+ mature myeloma cells, and this phenotypic classification was compatible with the morphology. Immature myelomac cells responded to interleukin 6 (IL-6) to proliferate, while mature myeloma cells did not show any prolifeartive activity. In order to clarify the differentiation pathway of plasma cells, we investigated the differentiation pathway of normal plasma cells in the bone marrow. We sorted the early plasma cells from peripheral blood mononuclear cells, and cultured them with bone marrow stromal cells in vitro. These cells were shown to differentiate to mature plasma cells escaping from apoptosis. IL-6 produced by bone marrow stromal cells suppressed the induction of their apoptosis. Along with differentiation of early (immature) plasma cells, the expression of MPC-1 antigen was induced rapidly. These data were suggestive that IL-6-induced differentiation was followed by the induction of MPC-1 gene expression. On the other hand, immature myeloma cells are considered to be clonogenic myeloma cells and they could not differentiate to mature cells but rather proliferate in response to IL-6. Therefore, clarifying the mechansm of MPC-1 gene induction by IL-6 will contribute to the understanding of dysdifferentiation of immature myeloma cells. We are now cloning cDNA of MPC-1 gene in order to clarify the mechanism of IL-6-induced MPC-1 gene expression.
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