BCR ABL P210 AND P190 CAUSE DISTINCT LEUKEMIA IN TRANSGENIC MICE/

DNA constructs encoding BCR/ABL P210 have been introduced into the mou se germ line using microinjection of one-cell fertilized eggs. Kinetic s of BCR/ABL P210 expression in transgenic mice were very similar to t hose of BCR/ABL P190 constructs in transgenic mice. mRNA transcripts w ere detectable early in embryonic development and also in hematopoieti c tissue of adult animals. Expression of BCR/ABL in peripheral blood p receded development of overt disease. P210 founder and progeny transge nic animals, when becoming ill. developed leukemia of B, T-lymphoid, o r myeloid origin after a relatively long latency period. In contrast, P190-transgenic mice exclusively developed leukemia of B-cell origin, with a relatively short period of latency. The observed dissimilaritie s are most likely due to intrinsically different properties of the P19 0 and P210 oncoproteins and may also involve sequences that control tr ansgene expression. The delayed progression of BCR/ABL P210-associated disease in the transgenic mice is consistent with the apparent indole nce of human chronic myeloid leukemia during the chronic phase. We con clude that, in transgenic models. comparable expression of BCR/ABL P21 0 and BCR/ABL P190 results in clinically distinct conditions. (C) 1995 by The American Society of Hematology.