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Publication : Diverse hematological malignancies including hodgkin-like lymphomas develop in chimeric MHC class II transgenic mice.

First Author  Raffegerst SH Year  2009
Journal  PLoS One Volume  4
Issue  12 Pages  e8539
PubMed ID  20046882 Mgi Jnum  J:155936
Mgi Id  MGI:4418375 Doi  10.1371/journal.pone.0008539
Citation  Raffegerst SH, et al. (2009) Diverse hematological malignancies including hodgkin-like lymphomas develop in chimeric MHC class II transgenic mice. PLoS One 4(12):e8539
abstractText  A chimeric HLA-DR4-H2-E (DR4) homozygous transgenic mouse line spontaneously develops diverse hematological malignancies with high frequency (70%). The majority of malignancies were distributed equally between T and B cell neoplasms and included lymphoblastic T cell lymphoma (LTCL), lymphoblastic B cell lymphoma (LBCL), diffuse large B cell lymphoma (DLBCL), the histiocyte/T cell rich variant of DLBCL (DLBCL-HA/T cell rich DLBCL), splenic marginal zone lymphoma (SMZL), follicular B cell lymphoma (FBL) and plasmacytoma (PCT). Most of these neoplasms were highly similar to human diseases. Also, some non-lymphoid malignancies such as acute myeloid leukemia (AML) and histiocytic sarcoma were found. Interestingly, composite lymphomas, including Hodgkin-like lymphomas, were also detected that had CD30(+) Hodgkin/Reed-Sternberg (H/RS)-like cells, representing a tumor type not previously described in mice. Analysis of microdissected H/RS-like cells revealed their origin as germinal center B cells bearing somatic hypermutations and, in some instances, crippled mutations, as described for human Hodgkin lymphoma (HL). Transgene integration in an oncogene was excluded as an exclusive driving force of tumorigenesis and age-related lymphoma development suggests a multi-step process. Thus, this DR4 line is a useful model to investigate common molecular mechanisms that may contribute to important neoplastic diseases in man.
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