Leukemogenesis of b2a2-type p210 BCR/ABL in a Bone Marrow Transplantation Mouse Model Using a Lentiviral Vector

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Author(s)

    • Uchida Naoya
    • Department of Molccular and Medical Genetics, Graduate School of Medicine, Nippon Medical School|Department of Pathophysiological Management/Medical Oncology, Graduate School of Medicine, Nippon Medical School
    • Hanawa Hideki
    • Department of Molccular and Medical Genetics, Graduate School of Medicine, Nippon Medical School
    • Dan Kazuo
    • Department of Pathophysiological Management/Medical Oncology, Graduate School of Medicine, Nippon Medical School
    • Inokuchi Koiti
    • Department of Pathophysiological Management/Medical Oncology, Graduate School of Medicine, Nippon Medical School
    • Shimada Takashi
    • Department of Molccular and Medical Genetics, Graduate School of Medicine, Nippon Medical School

Abstract

The BCR/ABL fusion oncogene found in Philadelphia-positive leukemia exists in three principle forms: p190, p210 and p230. P210 BCR/ABL is commonly found in patients with chronic myelogenous leukemia (CML) and is further categorized into b3a2 or b2a2 subtypes on the basis of the BCR breakpoint. Although these 2 subtypes may be clinically heterogeneous, only the b3a2 BCR/ABL gene has been extensively studied at the molecular and cellular levels. In the present study, we compared the in vivo leukemogenic activity of the b3a2 and b2a2 BCR/ABL genes by using lentiviral transduction/transplantation mouse models. Lineage-depleted bone marrow cells of BALB/c mice were transduced with a lentiviral vector including either b2a2 or b3a2 BCR/ABL cDNA and then transplanted into lethally irradiated mice. In this model, p210 BCR/ABL subtype developed only B220<sup>+</sup>, CD3e<sup>-</sup>, Gr1<sup>-</sup>, and Mac1<sup>-</sup> B-cell acute lymphoblastic leukemia but not myeloid leukemia. There were no differences in the incidence of leukemogenesis, the white blood cell count, the percentage of blast cells, or the survival rates between the b2a2 and b3a2 groups. We have demonstrated that b2a2-type BCR/ABL has leukemogenic activity similar to that of b3a2-type BCR/ABL.<br>

Journal

  • Journal of Nippon Medical School

    Journal of Nippon Medical School 76(3), 134-147, 2009

    The Medical Association of Nippon Medical School

Codes

  • NII Article ID (NAID)
    130004146984
  • Text Lang
    ENG
  • ISSN
    1345-4676
  • Data Source
    J-STAGE 
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