EXPRESSION OF MULTIDRUG-RESISTANT GENE (MDR-1 P-GLYCOPROTEIN) IN A MEGAKARYOBLASTIC CELL-LINE, CMK, AND ITS ENHANCEMENT DURING MEGAKARYOCYTIC DIFFERENTIATION/

Multidrug resistance is a severe clinical problem in the chemotherapy of malignant disease. Acute megakaryoblastic leukemia (AMKL) is a rare form of childhood leukemia, and is often resistant to many anti-cance r chemotherapeutic drugs. Here we report the expression of the mdr-1/P -glycoprotein in a cell line, CMK, established from a patient with AMK L. Expression of mdr-1 mRNA in CMK11-5 cells, a well differentiated su bline, was higher than in CMK6 cells, a poorly differentiated subline. The level of P-glycoprotein was also higher in CMK11-5 cells. The cyt okines interferon-gamma (IFN-gamma), GM-CSF and IL-3, which were shown to induce megakaryocytic differentiation of CMK cells, enhanced the e xpression of the mdr-1 mRNA and levels of P-glycoprotein. These result s imply that differentiated megakaryocytic cells may have higher level s of the P-glycoprotein expression, suggesting a possible normal physi ological function of P-glycoprotein in mature megakaryocytes.