Molecular mechanism of MLL mutant-induced MDS

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591367
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Chiba University
• Principal Investigator: SASHIDA Goro 千葉大学, 医学(系)研究科(研究院), 助教 (70349447)
• Co-Investigator(Renkei-kenkyūsha): IWAMA Atsushi 千葉大学, 大学院医学研究院, 教授 (70244126)
• Project Period (FY): 2011 – 2013
• Keywords: MLL-PTD / RUNX1 / 骨髄異形成症候群 / 急性骨髄性白血病 / 国際情報交換

Research Abstract

Given that MLL-PTD regulates the expression of RUNX1 mutants at protein level, we generated a novel MDS/AML mouse model by utilizing MLL-PTD knock-in mouse and Runx1 heterozygous mouse or RUNX1 mutants. We also demonstrated how MLL-PTD and RUNX1 mutants collaborated to induce the development of MDS and promote AML following MDS.

Research Products

• [Journal Article] Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells (2012)
  • Author(s): Zhang Y, Yan X, Sashida G, Zhao X, Rao Y, Goyama S, Whitman SP, Zorko N, Bernot K, Conway RM, Witte D, Wang QF, Tenen DG, Xiao Z, Marcucci G, Mulloy JC, Grimes HL, Caligiuri MA, and Huang G, equal contribution
  • Journal Title: Blood Volume: 120(5) Pages: 1118-29
  • DOI: 10.1182/blood-2012-02-412379
  • Peer Reviewed
• [Presentation] Modeling and Targeting MLL-PTD/RUNX1 Related MDS/AML In Mouse (2013)
  • Author(s): Yue Zhang, Xiaomei Yan, Aili Chen, Goro Sashida, Zhijian Xiao, and Gang Huang
  • Organizer: アメリカ血液学会
  • Place of Presentation: ニューオリンズ、米国(Blood 2013 122:2746)
  • Year and Date: 2013-12-06
• [Presentation] Modeling MLL-PTD Related Myelodysplastic Syndromes in Mouse (2012)
  • Author(s): Xiaomei Yan, Yue Zhang, Goro Sashida, Aili Chen, Xinghui Zhao, Susan Whitman, Qianfei Wang, Michael A. Caligiuri, Zhijian Xiao, and Gang Huang
  • Organizer: アメリカ血液学会
  • Place of Presentation: アトランタ、米国(Blood 2012; 120: 2811)
  • Year and Date: 2012-12-08
• [Presentation] Stress Hematopoiesis Reveals Abnormal Control of Self-Renewal, Lineage-Bias and Myeloid Differentiation in Mll Partial Tandem Duplication (Mll-PTD) Hematopoietic Stem/Progenitor Cells (2012)
  • Author(s): Yue Zhang, Xiaomei Yan, Goro Sashida, Xinghui Zhao, Yalan Rao, Susumu Goyama, Susan Whitman, Nicholas Zorko, Kelsie M. Bernot, Rajeana M. Conway, David Witte, Qianfei Wang, Daniel G Tenen, Zhijian Xiao, Guido Marcucci, James C. Mulloy, H. Leighton Grimes, Michael A. Caligiuri, and Gang Huang
  • Organizer: アメリカ血液学会
  • Place of Presentation: アトランタ、米国(Blood 2012; 120: 3501)
  • Year and Date: 2012-12-08
• [Presentation] MLL-PTD Causes Hypomorph Condition of CBF Complex (RUNX1/CBFβ) and Predisposes the Abnormal Hematopoietic Stem and Progenitor Cells (HSPCs) to Clonal Expansion (2011)
  • Author(s): Yue Zhang, Xiaomei Yan, Goro Sashida, Xinghui Zhao, Yalan Rao, Susumu Goyama, Susan P. Whitman, Nicholas Zorko, Kelsie M. Bernot, David Witte, Qian-fei Wang, Daniel G. Tenen, Zhijian Xiao, Guido Marcucci, James C. Mulloy, Michael A Caligiuri, and Gang Huang
  • Organizer: アメリカ血液学会
  • Place of Presentation: サンディエゴ、米国(Blood 2011; 118: 2801)
  • Year and Date: 2011-12-10