Opposing impact of AID deficiency on BCL-2 and IL-6 driven B-lymphoma development in BALB/c mice
  
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DOI:10.46701/APJBG.2017042017044
KeyWord:genetically engineered mouse model (GEMM) of human cancer, B-cell leukemia 2 (BCL-2), interleukin 6 (IL-6), activation-induced cytidine deaminase (AID)
           
AuthorInstitution
Chunyan Gu Department of Pathology, Carver College of Medicine, Iowa City,The University of Iowa,Iowa City, Iowa, 52242, USA;
Xuefang Jing Department of Pathology, Carver College of Medicine, Iowa City,The University of Iowa,Iowa City, Iowa, 52242, USA;
Ye Yang School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023,China.
Siegfried Janz Department of Pathology, Carver College of Medicine, Iowa City,The University of Iowa,Iowa City, Iowa, 52242, USA.
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Abstract:
      Activation-induced cytidine deaminase (AID), an essential enzymatic activity required for somatic hypermutation and immunoglobulin class switch recombination in the course of normal B-lymphocyte development, has been implicated in the initiation and promotion of malignant B-cell tumors by virtue of a complex mechanism that includes the generation of oncogene-activating genomic rearrangements and the introduction of point mutations in cancer genes. Here, we use transgenic mouse models of B-cell lymphoma driven by the pro-inflammatory cytokine, interleukin 6 (IL-6), or the survival-enhancing oncoprotein, B-cell leukemia 2 (BCL-2), to evaluate the impact of loss of AID on neoplastic B-cell development. We show that AID deficiency accelerates BCL-2 induced lymphoma but delays IL-6 induced lymphoma. This led us to conclude that AID may function as tumor suppressor or tumor promoter, depending on the genetic context. Elucidating the mechanism of AID's dual function during malignant B-cell transformation may be important for new approaches to tumor treatment and prevention.
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