| Project/Area Number |
14571002
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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 | Nippon Medical School |
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Principal Investigator |
OGATA Kiyoyuki Nippon Medical School, Department of Medicine, Associate Professor, 医学部, 助教授 (20169171)
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| Co-Investigator(Kenkyū-buntansha) |
TAMURA Hideto Nippon Medical School, Department of Medicine, Clinical & Research Fellow, 医学部, 助手 (70256949)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | myelodysplastic syndromes / blasts / biological characteristics / phenotype / hematopoietic stem cells / フローサイトメトリー / 骨髄異形成症侯群 / CD7 |
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| Research Abstract |
We prepared blast-rich specimens (using a new density-centrifugation reagent for harvesting blasts) from blood and marrow samples of many patients with myelodysplastic syndromes(MDS) or acute leukemia transformed from MDS(AL-MDS) and examined blast characteristics. Key findings are the following. (1)The blasts from almost all cases were CD34^+CD38^+HLA-DR^+CD13^+CD33^+, regardless of the disease subtype. The cytochemical reaction for myeloperoxidase was negative in 58% of the cases. Thus, the blast phenotype is more immature in MDS than in de novo acute myeloid leukemia. (2)The blasts often coexpressed stem-cell antigens and late-stage myeloid antigens asynchronously, but rarely expressed T- and B-lymphoid cell-specific antigens. (3)Markers for myeloid-cell maturation (CD10 and CD15) were more prevalent on blasts from low-risk MDS (refractory anemia [RA] and RA with ringed sideroblasts), while markers for myeloid-cell immaturity (CD7 and CD117) were more prevalent on blasts from high-r
… More
isk MDS (chronic myelomonocytic leukemia, RA with excess blasts [RAEB] and RAEB in transformation) and AL-MDS. A shift to a more immature phenotype of blasts, accompanying disease progression, was also documented by sequential phenotyping of the same patients. (4)When the blast percentage in the marrow increased, cases whose blasts expressed CD7,CD56 and CD117 increased whereas cases whose blasts expressed CD10,CD11b and CD15 decreased. The marrow blast percentages where the blast immunophenotype changed were 5%,10% and 20%. Blast immunophenotypes have the potential to provide a biological basis for the present MDS classifications. (5)CD7-positivity of blasts was an independent variable for a poor prognosis in MDS. (6)CD45^-CD34^-CD38^-Lin^- blastoid cells having chromosomal aberration were detected in some patients. When co-cultured with stroma cells, CD45^-CD34^-CD38^-Lin^- cells showed only weak potential for proliferation/differentiation, yet differentiated into CD34^+ cells and then mature myeloid cells. This cell population represents the most immature immunophenotype so far identified in the hematopoietic lineage. Less
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