Oncogene Activation in Human Myeloid Leukemia¹

We have studied by means of DNA-mediated gene transfer the activation of protooncogenes in human myeloid leukemias that represent various stages of myeloid differentiation. DNA from three cell lines, HL-60 (promyelocytic leukemia), Rc2a (myelomonocytic leukemia), and KG-1 (acute myeloblastic leukemia), was capable of transforming NIH/3T3 cells. Hybridization analysis indicated that, in all three tumor cell lines, the N-ras oncogene was activated. The cell lines U-937 (“histiocytic lymphoma”) and K-562 (erythroblastic leukemia) yielded no transforming DNA. Fresh leukemia cells derived from an acute myelomonocytic leukemia patient and from a juvenile chronic myelogenous leukemia patient contained an activated N-ras and c-Ki-ras oncogene, respectively. DNA from some other myelogenous leukemia patients was not able to transform NIH/3T3 cells.

Our results indicate that hematopoietic tumors of the myeloid lineage may contain oncogenes active in NIH/3T3 cell transformation and that, in particular, the N-ras oncogene may be activated in tumors representing various stages of maturation.