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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3897-3904. Prepublished online as a Blood First Edition Paper on January 29, 2004; DOI 10.1182/blood-2003-11-4026. This Article Full Text (PDF) All Versions of this Article: 2003-11-4026v1 103/10/3897    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jiang, X. Articles by Eaves, C. Search for Related Content PubMed PubMed Citation Articles by Jiang, X. Articles by Eaves, C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted November 25, 2003 Accepted January 18, 2004 Deregulated Expression in Ph+ Human Leukemias of AHI-1, a Gene Activated by Insertional Mutagenesis in Mouse Models of Leukemia Xiaoyan Jiang*, Yun Zhao, Wing Yiu Chan, Suzanne Vercauteren, Emily Pang, Sean Kennedy, Frank Nicolini, Allen Eaves, and Connie Eaves Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada Hematology Department, Hospital E. Herriot, Lyon, France Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; Departments of Medicine, Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada; Departments of Medicine, Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada * Corresponding author; email: xjiang{at}bccancer.bc.ca. Ahi-1/AHI-1 encodes a family of protein isoforms containing one SH3 domain and multiple WD40-repeat domains. The function of these proteins is unknown but involvement in leukemogenesis has been suggested by the high frequency of Ahi-1 mutations seen in certain virus-induced murine leukemias. Here we show that in both mice and humans, Ahi-1/AHI-1 expression is highest in the most primitive hematopoietic cells with specific patterns of down-regulation in different lineages. Cells from patients with chronic myeloid leukemia (n=28) show elevated AHI-1 transcripts in all disease phases and, in chronic phase, in the leukemic cells at all stages of differentiation, including quiescent (G0) CD34+ cells as well as terminally differentiating cells. In the most primitive lin--CD34+CD38- CML cells, transcripts for the 2 shorter isoforms of AHI-1 are also increased. Although 15 of 16 human lymphoid and myeloid leukemic cell lines showed aberrant control of AHI-1 expression, this was not seen in blasts obtained directly from patients with acute Ph- leukemia (n=15). Taken together, our results suggest that down-regulation of AHI-1 expression is an important conserved step in primitive normal hematopoietic cell differentiation and that perturbations in AHI-1 expression may contribute to the development of specific types of human leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: TEL-AML1 and BCR-ABL: different leukemias, similar questions Linda Stork Blood 2004 103: 3611-3612. [Full Text] [PDF] This article has been cited by other articles: B. K. Han, J. G. Jung, J. Nam, J. K. Moon, J. N. Kim, S. I. Lee, J. K. Kim, H. Kim, and J. Y. Han Identification of the Major Proteins Produced by Cultured Germline Stem Cells in Chicken J Androl, November 1, 2009; 30(6): 690 - 702. [Abstract] [Full Text] [PDF] E. Kennah, A. Ringrose, L. L. Zhou, S. Esmailzadeh, H. Qian, M.-w. Su, Y. Zhou, and X. 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