Clonal nature of mink cell focus-inducing virus-induced AKR leukemia: studies with X-chromosome inactivation cellular mosaicism.

The number of cells from which murine thymic leukemias (thymomas) develop after neonatal injection with a mink cell focus-inducing recombinant virus was studied in AKR mice heterozygous at the X-linked phosphoglycerate kinase (PGK) locus. Because only one of the two X-chromosomes is active in XX somatic cells, thymic leukemias that are clonal should display either type A or type B PGK but not both, whereas those with a multicellular origin may exhibit both enzymes. In 23 of 25 animals studied, thymomas expressed exclusively (11 animals) or predominantly (12 animals) a single enzyme in contrast to normal tissue which expressed both enzyme types in approximately equal ratios. In the 12 thymomas expressing a minor enzyme component, the predominant enzyme in the original tumor always predominated in the thymomas arising in animals transplanted with the original tumors, indicating that this minor PGK component was not contributed by malignant cells. The results indicate that the great majority of recombinant virus-induced AKR leukemias are clonal.