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Carcinogenesis, Vol. 23, No. 6, 1079-1085, June 2002
© 2002 Oxford University Press

CARCINOGENESIS

Myeloid, B and T lymphoid and mixed lineage thymic lymphomas in the irradiated mouse

Emma Boulton, Helen Cleary and Mark Plumb,1

MRC Radiation and Genome Stability Unit, Chilton Didcot, Oxfordshire OX11 ORD, UK

Thymic lymphoma is a very common spontaneous and/or induced malignancy in both inbred mice and in transgenic mouse models of human cancer. Although a thymic lymphoma is defined as thymus-dependent T-cell malignancy, diagnostic criteria vary between studies and considerable heterogeneity has been reported. To define and classify the thymic lymphomas that arose in our study of X-irradiated (CBA/HxC57BL/6)F1, F1 backcross and F1 intercross mice, 66 thymic lymphomas were immunogenotyped for immunoglobulin heavy chain (IgH) and T-cell receptor ß (TCRß) gene rearrangements, and/or analysed for expression of lineage-specific markers and allelic loss on chromosome 4. The data indicate that 33% of the thymic lymphomas are very similar to mouse radiation-induced acute myeloid (AML) and mixed lineage (IgHR, TCRßG) pre-B lympho-myeloid (L-MLs) leukaemias, 33% are mixed lineage (IgHR, TCRßR) B/T lymphoid and <33% can be described as single lineage (IgHG, TCRßR) T-cell malignancies. As the myeloid and L-ML leukaemias are not thymus-dependent this suggests that a malignant myeloid or pre-B lympho-myeloid cell can colonize the spleen to give an AML or L-ML leukaemia, or can colonize the thymus where TCRß gene rearrangement(s) may be induced to give the mixed lineage thymic lymphomas. Thus, assuming the single lineage T-cell thymic lymphomas fulfil the criteria of a thymus-dependent T-cell malignancy, thymic lymphomas are comprised of at least three distinct malignancies.


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