• Acute Progression of BCR-FGFR1 Induced Murine B-Lympho/Myeloproliferative Disorder Suggests Involvement of Lineages at the Pro-B Cell Stage

      Ren, MingQiang; Tidwell, Josephine A.; Sharma, Suash; Cowell, John K.; GHSU Cancer Center; Department of Pathology (2012-06-6)
      Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that both showed bi-lineage involvement of myeloid and B-cells, splenomegaly, leukocytosis and bone marrow hypercellularity. A CD19+ IgMâ CD43+ immunophenotype was seen both in primary tumors and two cell lines derived from these tumors. In all primary tumors, subpopulations of these CD19+ IgMâ CD43+ were also either B220+ or B220â , suggesting a block in differentiation at the pro-B cell stage. The B220â phenotype was retained in one of the cell lines while the other was B220+. When the two cell lines were transplanted into syngeneic mice, all animals developed the same B-lymphoblastic leukemia within 2-weeks. Thus, the murine model described here closely mimics the human disease with bilineage myeloid and B-cell leukemia/lymphoma which provides a representative model to investigate therapeutic intervention and a better understanding of the etiology of the disease.
    • Inactivation of the WASF3 gene in prostate cancer cells leads to suppression of tumorigenicity and metastases

      Teng, Yong; Ren, MingQiang; Cheney, Richard; Sharma, Shruti; Cowell, John K.; GHSU Cancer Center; Department of Pathology (2010-09-28)
      Background:: The WASF3 protein is involved in cell movement and invasion, and to investigate its role in prostate cancer progression we studied the phenotypic effects of knockdown in primary tumors and cell lines.
    • NF-kB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors

      McCarthy, Brian A.; Yang, Liqun; Ding, Jane; Ren, MingQiang; King, William; ElSalanty, Mohammed; Zakhary, Ibrahim; Sharawy, Mohamed; Cui, Hongjuan; Ding, Han-Fei; et al. (2012-05-29)
      Background: Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines.