Expression of Multidrug Resistant Gene (mdr-1/P-glycoprotein) in a Megakaryoblastic Cell Line, CMK, and its Enhancement During Megakaryocytic Differentiation

Abstract

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-cancer chemotherapeutic drugs. Here we report the expression of the mdr-1 IIP-glycoprotein in a cell line, CMK, established from a patient with AMKL. Expression of mdr-1 mRNA in CMK11-5 cells, a well differentiated subline, was higher than in CMK6 cells, a poorly differentiated subline. The level of P-glycoprotein was also higher in CMK11-5 cells. The cytokines interferon-γ (IFN-γ), GM-CSF and IL-3, which were shown to induce megakaryocytic differentiation of CMK cells, enhanced the expression of the mdr-1 mRNA and levels of P-glycoprotein. These results imply that differentiated megakaryocytic cells may have higher levels of the P-glycoprotein expression, suggesting a possible normal physiological function of P-glycoprotein in mature megakaryocytes.

Key Words:

• mdr-1
• P-glycoprotein
• Megakaryocytic cell line
• differentiation