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AID-induced T-Iymphoma or B-leukemia/lymphoma in a mouse BMT model.(ORIGINAL ARTICLE)(activation-induced cytidine deaminase)(bone marrow transplantation)
Ist Teil von
Leukemia, 2010-05, Vol.24 (5), p.1018
Ort / Verlag
Nature Publishing Group
Erscheinungsjahr
2010
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
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, Notchl was constitutively activated in most cases. Importantly, truncations of Ebfl 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 Keywords: AID; BMT; T-lymphoma; B-leukemia/lymphoma