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-cancer chemotherapeutic drugs. Here we report the expression of the mdr-1/P-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-gamma (IFN-gamma), 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.
Department of Pediatrics, School of Medicine, Chiba University, Japan.
T
T
Sato
S
S
Ota
H
H
Kakuda
N
N
Miura
H
H
Niimi
M
M
Ito
T
T
Asai
T
T
Tsuruo
A
A
Fuse
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000235:genetics; D018432:Drug Resistance, Multiple; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005796:Genes; D006801:Humans; D007124:Immunoenzyme Techniques; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics*; D008533:Megakaryocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016207:Cytokines; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm