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

作者：Komeno Y; Kitaura J; Watanabe Okochi N; Kato N; Oki T; Nakahara F; Harada Y; Harada H; Shinkura R; Nagaoka H; Hayashi Y; Honjo T; Kitamura T^*

来源：Leukemia, 2010, 24(5): 1018-1024.

DOI：10.1038/leu.2010.40

• AID
• BMT
• T-lymphoma
• B-leukemia/lymphoma

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. Leukemia (2010) 24, 1018-1024; doi:10.1038/leu.2010.40; published online 1 April 2010

• 出版日期2010-5
• 单位河北医科大学