AID-induced T-lymphoma or B-leukemia/lymphoma in a mouse BMT model

Leukemia. 2010 May;24(5):1018-24. doi: 10.1038/leu.2010.40. Epub 2010 Apr 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Southern
  • Blotting, Western
  • Bone Marrow Transplantation*
  • Cytidine Deaminase / physiology*
  • Disease Models, Animal*
  • Flow Cytometry
  • Lymphoma, T-Cell / etiology*
  • Lymphoma, T-Cell / pathology
  • Mice
  • Mice, Inbred C57BL
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / etiology*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • RNA, Messenger
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase