Upregulated hoxC4 induces CD14 expression during the differentiation of acute promyelocytic leukemia cells.
Homeobox (hox) genes encode transcription factors which are critically involved in embryonic development. The 39 different hox genes are organized into four unlinked chromosomal gene clusters (hoxA-D) in mammals and a number of studies have suggested that hox genes play important roles in human leukemogenesis. Acute promyelocytic leukemia (APL) cells carrying the PML-RARa fusion protein, respond well by differentiating in their response to an all-trans-retinoic acid (ATRA) treatment. We examined the expression of the individual hox genes during this differentiation. Besides the constitutive expression of hoxA9 and no expression of hoxB7, the expression of hoxC4 increased significantly during differentiation of NB4 cells (PML-RAR(alpha)+). We also examined the expression of hoxC4 in bone marrow cells from APL patients and found that the hoxC4 expression was reproducibly induced during an ATRA treatment. To further examine this finding, HoxC4 was stably expressed in NB4 cells by retroviral transduction. The NB4 cells expressing HoxC4 showed differentiated phenotypes including a CD14 expression, which strongly suggests that upregulated hoxC4 is functionally involved in NB4 cell differentiation in response to ATRA. Upregulation of CD14 is at the transcription level and mediated by the homeodomain of the HoxC4.
Kim
Dong-Yeon
DY
Department of Molecular Cell Biology, SBRI, Sungkyunkwan University School of Medicine, Suwon, Korea.
Choi
So-Jung
SJ
Kim
Sun-Hee
SH
Chung
Hee-Yong
HY
Yi
Seok
S
Kim
Dong-Wook
DW
Kim
Chun-Chu
CC
Han
Tae-Hee
TH
D000970:Antineoplastic Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D015973:Gene Expression Regulation, Leukemic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D020298:U937 Cells; D015854:Up-Regulation
D000970:Antineoplastic Agents; C098691:HOXC4 protein, human; D018398:Homeodomain Proteins; D018950:Lipopolysaccharide Receptors; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin