Clonal nature of spontaneous AKR leukemia: studies utilizing the X-linked enzyme phosphoglycerate kinase

AKR mice heterozygous at the X-linked phosphoglycerate kinase (PGK) locus were used in experiments to determine the number of cells from which spontaneous thymic leukemias (thymomas) develop. 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, while those that are multicellular in origin may exhibit both enzymes. Spontaneous thymomas from 19 PGK heterozygous animals expressed exclusively (11 tumors) or predominantly (8 tumors) a single enzyme in contrast to non-malignant tissue from these animals which expressed both enzyme types in approximately equal ratios. When primary tumors expressing a single or predominant enzyme type were transplanted, the transplanted tumors invariably displayed the PGK phenotype that predominated in the initial tumor indicating that the minor PGK component was not contributed by malignant cells. These results indicate that spontaneous AKR leukemias are clonal.