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Cloning and Developmental Expression of the Murine Homolog of the Acute Leukemia Proto-Oncogene Af4

  1. Author:
    Baskaran, K.
    Erfurth, F.
    Taborn, G.
    Copeland, N. G.
    Gilbert, D. J.
    Jenkins, N. A.
    Iannaccone, P. M.
    Domer, P. H.

  2. Author Address

    Domer PH UNIV CHICAGO DEPT PATHOL 5841 S MARYLAND AVE CHICAGO, IL 60637 USA UNIV CHICAGO DEPT PATHOL CHICAGO, IL 60637 USA NORTHWESTERN UNIV SCH MED DEPT PEDIAT CHILDRENS MEM INST EDUC & RES CHICAGO, IL 60614 USA FREDERICK CANC RES & DEV CTR ABL BASIC RES PROGRAM FREDERICK, MD 21702 USA
    1. Year: 1997
  2. Journal: Oncogene
    1. 15
    2. 16
    3. Pages: 1967-1978
  4. Type of Article: Article
  1. Abstract:

    AF4 is the 4q21 gene involved in the acute lymphoblastic leukemia associated t(4;11)(q21;q23) where it forms a fusion gene with MLL, In order to gain insight into AF4's role in leukemogenesis we have studied its functional domains and expression pattern during murine development, We have cloned the murine homolog, Af4. We have demonstrated that 5' half of Af4 encodes a region with transcriptional transactivation activity which is disrupted by the t(4;11) in human leukemias, We have also localized the murine AF4 protein to the nucleus supporting a role for AF4 in transcription, The developmental expression pattern of Af4 was determined in situ hybridization and suggests Af4 plays an important role in the development of the hematopoietic, cardiovascular, skeletal and central nervous systems, A repeating pattern of Af4 expression in development is downregulation with differentiation of a tissue, Among the cell types where this pattern of down-regulation is noted are B-lymphocytes. These findings raise the possibility that the disruption of normal AF4 function by the translocation may contribute to leukemogenesis. [References: 57]

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