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MYC Responsible for down-Regulation of CD33 Expression in Human Myeloma Cells

مؤلف البحث
Karim Shamsasenjan, Ken-ichiro Otsuyama, Mohd S. Iqbal, Maged S. Mahmoud, Michio M. Kawano
تاريخ البحث
مجلة البحث
Blood
المشارك في البحث
الناشر
The American Society of Hematology
عدد البحث
112 (11)
موقع البحث
https://doi.org/10.1182/blood.V112.11.5116.5116
سنة البحث
2008
صفحات البحث
5116
ملخص البحث

Human myeloma cells from about 10% of cases with multiple myeloma expressed CD33 and have monocytoid morphology with convoluted nuclei, and all these patients had no increase in serum CRP values. In CD33(+) myeloma cells as well as myeloma cell lines, CD33 expression levels were correlated with the increased expression levels of CEBPA (C/EBPα) gene. This correlation was confirmed by the finding that transfection with the CEBPA gene induced CD33 expression in a CD33(−) myeloma cell line. As suggested by the lack of an increase in serum CRP values in CD33(+) myelomas, IL-6 down-regulated the expression of CD33 in CD33(+) myeloma cell lines along with the down-regulation of CEBPA gene expression. Cucurbitacin I (STAT3 inhibitor) but not U0126 (MAPK inhibitor) could abolish the effect of IL-6. Furthermore, IL-6 up-regulated the expression of MYC via STAT3 phosphorylation and MYC bound to the promoter region of CEBPA gene followed by the down-regulation of the CEBPA expression. It was confirmed that introduction of shRNA for MYC into a CD33(+) myeloma cell line blocked the IL6-induced down-regulation of CD33 and CEBPA expression. Therefore, these results indicate that IL-6 can reverse the expression level of CD33 by up-regulating MYC followed by the down-regulation of CEBPA expression.