Diverse Hematological Malignancies Including Hodgkin-Like Lymphomas Develop in Chimeric MHC Class II Transgenic MiceReportar como inadecuado




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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.



Autor: Silke H. Raffegerst , Gabriele Hoelzlwimmer, Sandra Kunder, Josef Mysliwietz, Leticia Quintanilla-Martinez, Dolores J. Schendel

Fuente: http://plos.srce.hr/



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