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FIP1L1 presence in FIP1L1-RARA or FIP1L1-PDGFRA differentially contributes to the pathogenesis of distinct types of leukemia
Title: | FIP1L1 presence in FIP1L1-RARA or FIP1L1-PDGFRA differentially contributes to the pathogenesis of distinct types of leukemia |
Authors: | Iwasaki, Junko Browse this author | Kondo, Takeshi Browse this author →KAKEN DB | Darmanin, Stephanie Browse this author | Ibata, Makoto Browse this author | Onozawa, Masahiro Browse this author →KAKEN DB | Hashimoto, Daigo Browse this author | Sakamoto, Naoya Browse this author →KAKEN DB | Teshima, Takanori Browse this author →KAKEN DB |
Keywords: | FIP1L1 | RARA | PDGFRA | Leukemia |
Issue Date: | Sep-2014 |
Publisher: | Springer |
Journal Title: | Annals of Hematology |
Volume: | 93 |
Issue: | 9 |
Start Page: | 1473 |
End Page: | 1481 |
Publisher DOI: | 10.1007/s00277-014-2085-1 |
PMID: | 24763514 |
Abstract: | FIP1-like 1 (FIP1L1) is associated with two leukemogenic fusion genes: FIP1L1-retinoic acid receptor alpha (RARA) and FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA). Analyses of a series of deletion mutants revealed that the FIP1 motif in FIP1L1-RARA plays a pivotal role in its homodimerization and transcriptional repressor activity. However, in FIP1L1-PDGFRA, the C-terminal PDGFRA portion possesses the ability of forming a homodimer by itself, making FIP1L1 dispensable for constitutive activation of this kinase. Both the full-length and the C-terminal PDGFRA portion of FIP1L1-PDGFRA could transform the IL-3-dependent hematopoietic cell line, BAF-B03. Moreover, when either the full-length or the C-terminal PDGFRA portion of FIP1L1-PDGFRA was introduced in these cells, they grew in the absence of IL-3. The cells having the C-terminal PDGFRA portion of FIP1L1-PDGFRA, however, were partially IL-3 dependent, whereas the cells having the full-length FIP1L1-PDGFRA became completely IL-3 independent for their growth. Taken together, these results show that FIP1L1 differentially contributes to the pathogenesis of distinct types of leukemia. |
Rights: | The final publication is available at link.springer.com |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/59854 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 近藤 健
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