Abstract
Activation-induced cytidine deaminase (AID) diversifies immunoglobulin through somatic hypermutation (SHM) and class-switch recombination (CSR). AID-transgenic mice develop T-lymphoma, indicating that constitutive expression of AID leads to tumorigenesis. Here, we transplanted mouse bone marrow cells transduced with AID. Twenty-four of the 32 recipient mice developed T-lymphoma 2–4 months after the transplantation. Surprisingly, unlike AID-transgenic mice, seven recipients developed B-leukemia/lymphoma with longer latencies. None of the mice suffered from myeloid leukemia. When we used nude mice as recipients, they developed only B-leukemia/lymphoma, presumably due to lack of thymus. Analysis of AID mutants suggested that an intact form with SHM activity is required for maximum ability of AID to induce lymphoma. Except for a K-ras active mutant in one case, specific mutations could not be identified in T-lymphoma; however, Notch1 was constitutively activated in most cases. Importantly, truncations of Ebf1 or Pax5 were observed in B-leukemia/lymphoma. In conclusion, this is the first report on the potential of AID overexpression to promote B-cell lymphomagenesis in a mouse model. Aberrant expression of AID in bone marrow cells induced leukemia/lymphoma in a cell-lineage–dependent manner, mainly through its function as a mutator.
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Acknowledgements
We thank Dr Chiba (Tsukuba University, Ibaraki, Japan) for providing HPB-ALL cell line. We are grateful to Dr Dovie Wylie for her excellent language assistance. This work was supported by grants from the Ministry of Education, Science, Technology, Sports and Culture, Japan to TK.
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Komeno, Y., Kitaura, J., Watanabe-Okochi, N. et al. AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model. Leukemia 24, 1018–1024 (2010). https://doi.org/10.1038/leu.2010.40
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DOI: https://doi.org/10.1038/leu.2010.40
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