2002 Fiscal Year Final Research Report Summary
Gene expression profiles of acute leukemia and detection of new prognostic factors
| Project/Area Number |
13671059
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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 | Mie University |
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Principal Investigator |
KOBAYASHI Tohru Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00144246)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Gene expression profiling / DNA microarray / Acute promyelocytic leukemia / AML without maturation |
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| Research Abstract |
Acute myeloid leukemia (AML) has distinct subgroups characterized by different maturation and specific chromosomal translocation. In order to gain insight into the gene expression activities in AML, we carried out a gene expression profiling study with 21 acute AML samples using cDNA microarrays, focusing on acute promyelocytic leukemia with specific translocation t(15 ; 17)(q22 ; ql2) (French-American-British or FAB-M3 with t(15 ; 17)) and AML without maturation (FAB M1) characterized by morphologically and phenotypically immature AML blasts and no recurrent chromosomal abnormalities. Using a multivariate σ-classifier algorithm, we identified 33 strong feature genes that distinguish FAB-M3 with t(15 ; 17) from other AML samples, and 24 strong feature genes that classify FAB-M1. A direct comparison between FAB-M3 with t(15 ; 17) and FAB-M1 led to selection of 13 strong feature genes. Those genes include some known to be related to leukemogenesis and cell differentiation. RIN1, a gene in the ras pathway, was up-regulated in FAB-M3 with t(15 ; 17). Growth factor-binding protein 2 gene was down-regulated in FAB-M1. Huntingtin gene was up-regulated in FAB-M1. Others include syndecan 4, interleukin-2 receptor β, folate receptor β, low affinity immunoglobulin γ, Fc receptor II C precursor, insulin-like growth factor binding protein 2, and myeloperoxidase, which are involved in cell differentiation. Overexpression of myeloperoxidase in FAB-M3 cells with t(15 ; 17) compared to FAB-M1 cells is consistent with the conventional cytochemical staining pattern. Thus, the study revealed that a morphologically-defined FAB-M1 subtype has a distinct gene expression signature that contributes to its cell differentiation and proliferation as well as FAB-M3 with a recurrent cytogenetic abnormality ; t(15 ; 17)(q22 ; ql2).
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