Herbimycin A, an Inhibitor of Tyrosine Kinase, Prolongs Survival of Mice Inoculated with Myeloid Leukemia CI Cells with High Expression of v-abl Tyrosine Kinase

Herbimycin A, a benzoquinonoid ansamycin antibiotic, reduces intracellular phosphorylation by some tyrosine kinases, including v-abl. The mouse megakaryoblastic cell line CI expresses v-abl protein at high levels. Herbimycin A at about 20 ng/ml caused 50% inhibition of growth of CI cells but at 100 ng/ml scarcely affected the growth of another mouse leukemia cell line, Ml cells, or of normal bone marrow cells. Injection of 106 CI cells into nude mice resulted in death of all the mice within 30 days. Administration of herbimycin A significantly enhanced the survival of mice inoculated with CI cells but scarcely affected the survival of mice inoculated with Ml cells. These results suggest that herbimycin A and/or related compounds may be useful for treatment of some types of leukemia in which tyrosine kinase activity is implicated as a determinant of the oncogenic state.