Analysis of the differentiation control factor of leukemia, PRDM16 and physiological inhibitor LR11

• Project/Area Number: 24591380
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Toho University (2014); Chiba University (2012-2013)
• Principal Investigator: SHIMIZU Naomi 東邦大学, 医学部, 講師 (30375802)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: LR11 / G-CSF / 白血病 / 転写因子 / プロテアーゼ / WT1 / GATA1 / GATA2 / CD71

Outline of Final Research Achievements

We reported that LR11 is highly expressed in blasts of leukemia cells and the soluble form of LR11 (sLR11) is a modifier of leukemic cell migration. Moreover, the sLR11 levels are elevated by G-CSF. We evaluated the relation between transcriptional factors which regulate differentiation mechanism and LR11 under this background. It was not observed apparent association between the nuclear transcription factor and LR11. However, G-CSF, an important cytokine in the differentiation process, increased the TNF-α with soluble LR11 in leukemic cell lines. These results revealed the involvement of protease activation in the mechanism. The transcriptional factors which localize to cell membrane may be activated by proteases and play a key role in the relation between the transcription factors and LR11.

Research Products

• [Journal Article] Serum soluble LR11, a novel tumor derived biomarker associated with the outcome of patients with diffuse large B-cell lymphoma. (2015)
  • Author(s): Ohwada C, Yamazaki A, Kawaguchi T, Sugita Y, Takeuchi M, Shimizu N, Sakaida E, Takeda Y, Tsukamoto S, Muto T, Jiang M, Higashi M, Yokote K, Tamaru JI, Bujo H, Nakaseko C.
  • Journal Title: Leuk Lymphoma. Volume: 印刷中 Issue: 10 Pages: 1-4
  • DOI: 10.3109/10428194.2015.1016930
  • Peer Reviewed / Open Access
• [Journal Article] G-CSF induces the release of the soluble form of LR11, a regulator of myeloid cell mobilization in bone marrow (2014)
  • Author(s): Shimizu N, Nakaseko C, Jiang M, Nishii K, Yokote K, Iseki T, Higashi M, Tamaru J, Schneider WJ, Bujo H
  • Journal Title: Ann Hematol Volume: (印刷中) Issue: 7 Pages: 1111-1122
  • DOI: 10.1007/s00277-014-2033-0
  • Peer Reviewed / Open Access
• [Journal Article] Tetraspanin CD9 modulates ADAM17-mediated shedding of LR11 in leukocytes. (2014)
  • Author(s): Tsukamoto S, Takeuchi M, Kawaguchi T, Togasaki E, Yamazaki A, Sugita Y, Muto T, Sakai S, Takeda Y, Ohwada C, Sakaida E, Shimizu N, Nishii K, Jiang M, Yokote K, Bujo H, Nakaseko C.
  • Journal Title: Exp Mol Med. Volume: - Issue: 4 Pages: 46-89
  • DOI: 10.1038/emm.2013.161
  • Peer Reviewed / Open Access
• [Journal Article] Potential utility of serum soluble LR11 as a diagnostic biomarker for intravascular large B-cell lymphoma (2014)
  • Author(s): Kawaguchi T, Ohwada C, Takeuchi M, Shimizu N, Sakaida E, Takeda Y, Sakai S, Tsukamoto S, Yamazaki A, Sugita Y, Higashi M, Fujikawa K, Matsue K, Yokote K, Tamaru JI, Bujo H, Nakaseko C
  • Journal Title: Leuk Lymphoma Volume: (印刷中) Issue: 10 Pages: 2391-2394
  • DOI: 10.3109/10428194.2014.880430
  • Peer Reviewed / Open Access
• [Journal Article] Circulating LR11 is a novel soluble-receptor marker for early-stage clinical conditions in patients with non-Hodgkin's lymphoma. (2014)
  • Author(s): Fujimura K, Ebinuma H, Fukamachi I, Ohwada C, Kawaguchi T, Shimizu N, Takeuchi M, Sakaida E, Jiang M, Nakaseko C, Bujo H.
  • Journal Title: Clin Chim Acta. Volume: 430 Pages: 48-54
  • DOI: 10.1016/j.cca.2013.12.039
  • Peer Reviewed / Open Access
• [Journal Article] LR11 : a novel biomarker identified in follicular lymphoma (2013)
  • Author(s): Kawaguchi T, Ohwada C, Takeuchi M, Shimizu N, Sakaida E, Takeda Y, Sakai S, Tsukamoto S, Yamazaki A, Sugita Y, Jiang M, Higashi M, Yokote K, Tamura J, Bujo H, Nakaseko C
  • Journal Title: Br J Haematol Volume: 163(2) Issue: 2 Pages: 277-280
  • DOI: 10.1111/bjh.12467
  • Peer Reviewed
• [Journal Article] The soluble form of LR11 is a regulator of hypoxia-induced, uPAR-mediated adhesion of immature hematological cells (2013)
  • Author(s): Keigo Nishii, Chiaki Nakaseko, Meizi Jiang, Naomi Shimizu, Masahiro Takeuchi, Wolfgang Johann Schneider, and Hideaki Bujo
  • Journal Title: The Journal of Biological Chemistry Volume: 288(17) Issue: 17 Pages: 11877-11886
  • DOI: 10.1074/jbc.m112.442491
  • Peer Reviewed
• [Journal Article] Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias (2012)
  • Author(s): Sakai S, Nakaseko C, Takeuchi M, Ohwada C, Shimizu N, Tsukamoto S, Kawaguchi T, Jiang M, Sato Y, Ebinuma H, Yokote K, Iwama A, Fukamachi I, Schneider WJ, Saito Y, Bujo H.
  • Journal Title: Clin Chim Acta Volume: 96 Issue: 19-20 Pages: 542-1548
  • DOI: 10.1016/j.cca.2012.06.025
  • Peer Reviewed
• [Presentation] Tetraspanin CD9 inhibited ADAM17-mediated LR11 shedding in leukemia cell lines. (2013)
  • Author(s): Shokichi Tsukamoto, Masahiro Takeuchi, Takeharu Kawaguchi, Emi Togasaki, Atsuko Yamazaki, Yasumasa Sugita, Tomoya Muto, Shio Sakai, Yusuke Takeda, Chikako Ohwada, Naomi Shimizu, Emiko Sakaida, Keigo Nishii, Jiang Meizi, Tohru Iseki, Koutaro Yokote, Hideaki Bujo, Chiaki Nakaseko.
  • Organizer: The 55rd Annual Meeting og the American Society of Hematology
  • Place of Presentation: New Orleans(USA)
• [Presentation] Soluble form of LR11 is highly espressed on myeloid cells after G-CSF treatment. (2012)
  • Author(s): Naomi Shimizu, Hideaki Bujo, Shio Sakai, Shokichi Tsukamoto, Takeharu Kawaguchi, Yusuke Takeda, Chikako Ohwada, Masahiro Takeuchi, Emiko Sakaida, Keigo Nishi, Meizi Jiang, Chiaki Nakaseko.
  • Organizer: The 74th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: 京都国際会館
• [Presentation] Tetraspanin CD9 regulates ADAM17-mediated LR11 shedding in leukemia cells. (2012)
  • Author(s): Shokichi Tsukamoto, Masahiro Takeuchi, Atsuko Yamazaki, Takeharu Kawaguchi, Chikako Ohwada, Naomi Shimizu, Emiko Sakaida, Keigo Nishi, Meizi Jiang, Hideaki Bujo, Chiaki Nakaseko.
  • Organizer: The 74th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: 京都国際会館
• [Presentation] Soluble LR11, a novel acute leukemia marker, drastically induces WT1 mRNA expression together with synergic activation of GATAs, and the migration activity. (2012)
  • Author(s): Naomi Shimizu, Chiaki Nakaseko, Masahiro Takeuchi, Chikako Ohwada, Shokichi Tsukamoto, Keigo Nishii, Meiji Jiang, Koutaro Yokote, Isamu Fukamachi, Hideaki Bujo.
  • Organizer: The 53rd Annual Meeting of the American Society of Hematology
  • Place of Presentation: Atlanta(USA)