DF/HCC Program Affiliation

Leukemia
Cancer Immunology

Research Abstract

The central cells of the immune system include three lymphocyte populations: T cells, B cells, and natural killer cells. These lymphoid cells as well as all myeloid cells -- such as granulocytes, macrophages, megakaryocytes, and erythrocytes -- are derived from hematopoietic stem cells that are capable of self-renewal to maintain the immune system for life. Differentiation of hematopoietic stem cells into a variety of blood cell types involves sequential activation or silencing of several sets of genes. Understanding the molecular mechanism of differentiation and self-renewal in hematopoietic stem cells is important to establish new treatment strategies for cancer therapy.

Publications

• Raffel GD, Mercher T, Shigematsu H, Williams IR, Cullen DE, Akashi K, Bernard OA, Gilliland DG.Ott1(Rbm15) has pleiotropic roles in hematopoietic development.Proc Natl Acad Sci U S A 2007 Apr 3;104(14):6001-6.
  17376872
• Iwasaki H, Mizuno S, Arinobu Y, Ozawa H, Mori Y, Shigematsu H, Takatsu K, Tenen DG, Akashi K.The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages.Genes Dev 2006 Nov 1;20(21):3010-21.
  17079688
• Hirai H, Zhang P, Dayaram T, Hetherington CJ, Mizuno S, Imanishi J, Akashi K, Tenen DG.C/EBPbeta is required for 'emergency' granulopoiesis.Nat Immunol 2006 Jul;7(7):732-9.
  16751774
• Chan IT, Kutok JL, Williams IR, Cohen S, Moore S, Shigematsu H, Ley TJ, Akashi K, Le Beau MM, Gilliland DG.Oncogenic K-ras cooperates with PML-RAR{alpha} to induce an acute promyelocytic leukemia-like disease.Blood 2006 May 4.
  16675706
• Arinobu Y, Iwasaki H, Gurish MF, Mizuno S, Shigematsu H, Ozawa H, Tenen DG, Austen KF, Akashi K.Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis.Proc Natl Acad Sci U S A 2005 Dec 13;102(50):18105-10.
  16330751
• Rosenbauer F, Owens BM, Yu L, Tumang JR, Steidl U, Kutok JL, Clayton LK, Wagner K, Scheller M, Iwasaki H, Liu C, Hackanson B, Akashi K, Leutz A, Rothstein TL, Plass C, Tenen DG.Lymphoid cell growth and transformation are suppressed by a key regulatory ele
  16311598
• Iwasaki H, Mizuno S, Wells RA, Cantor AB, Watanabe S, Akashi K.GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages.Immunity 2003 Sep;19(3):451-62.
  14499119
• Iwasaki-Arai J, Iwasaki H, Miyamoto T, Watanabe S, Akashi K.Enforced granulocyte/macrophage colony-stimulating factor signals do not support lymphopoiesis, but instruct lymphoid to myelomonocytic lineage conversion.J Exp Med 2003 May 19;197(10):1311-22.
  12756267
• Miyamoto T, Iwasaki H, Reizis B, Ye M, Graf T, Weissman IL, Akashi K.Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment.Dev Cell 2002 Jul;3(1):137-47.
  12110174
• Okuno Y, Iwasaki H, Huettner CS, Radomska HS, Gonzalez DA, Tenen DG, Akashi K.Differential regulation of the human and murine CD34 genes in hematopoietic stem cells.Proc Natl Acad Sci U S A 2002 Apr 30;99(9):6246-51.
  11983914
• Traver D, Akashi K, Manz M, Merad M, Miyamoto T, Engleman EG, Weissman IL.Development of CD8alpha-positive dendritic cells from a common myeloid progenitor.Science 2000 Dec 15;290(5499):2152-4.
  11118150
• Miyamoto T, Weissman IL, Akashi K.AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation.Proc Natl Acad Sci U S A 2000 Jun 20;97(13):7521-6.
  10861016
• Akashi K, Traver D, Miyamoto T, Weissman IL.A clonogenic common myeloid progenitor that gives rise to all myeloid lineages.Nature 2000 Mar 9;404(6774):193-7.
  10724173
• Kondo M, Weissman IL, Akashi K.Identification of clonogenic common lymphoid progenitors in mouse bone marrow.Cell 1997 Nov 28;91(5):661-72.
  9393859
• Akashi K, Kondo M, von Freeden-Jeffry U, Murray R, Weissman IL.Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice.Cell 1997 Jun 27;89(7):1033-41.
  9215626