2012 Fiscal Year Final Research Report
A new mouse model of acute B lymphocytic leukemia (B-ALL)
| Project/Area Number |
23790434
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KURATA Morito 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (40451926)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 白血病 / 発がん / B細胞 |
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| Research Abstract |
Blnk (Bash/SLP-65) encodes an adaptor protein of the B-cell receptor signaling and functions as a tumor suppressor. Loss of function mutations of BLNK have been observed in human preB-ALL, however, only a subset of Blnk ko mice develop preB-ALL, suggesting that cooperative events with Blnk deficiency are required for complete leukemogenesis. Retroviral tagging was performed to identify the cooperative genes, and the Cebpb locus was the most frequent common integration site. Cebpb encodes two protein isoforms of LAP and LIP. Transgenic mice bearing LAP or LIP were generated, mated with Blnk ko mice, and transgenic expression of LAP significantly accelerated the ALL onset of Blnkko/ko mice. Moreover, significant decrease of mature B-cells and increase of IL-7Rα-positive fractions in the bone marrow of non-neoplastic Blnkko/ko/LAP tg mice was evident. Knockdown of C/EBP〓 in a human preB-ALL cell line lacking BLNK expression suppressed cellular growth. These results indicate that C/EBP〓 LAP promotes leukemogenesis in the absence of BLNK including human B-ALL.
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