Essential role for ALCAM gene silencing in megakaryocytic differentiation of K562 cells.
BACKGROUND
Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells. However, its role in hematopoietic differentiation has not previously been defined.


RESULTS
In this study, we show that ALCAM expression is silenced in erythromegakaryocytic progenitor cell lines. In agreement with this finding, the ALCAM promoter is occupied by GATA-1 in vivo, and a cognate motif at -850 inhibited promoter activity in K562 and MEG-01 cells. Gain-of-function studies showed that ALCAM clusters K562 cells in a process that requires PKC. Induction of megakaryocytic differentiation in K562 clones expressing ALCAM activated PKC-δ and triggered apoptosis.


CONCLUSIONS
There is a lineage-specific silencing of ALCAM in bi-potential erythromegakaryocytic progenitor cell lines. Marked apoptosis of ALCAM-expressing K562 clones treated with PMA suggests that aberrant ALCAM expression in erythromegakaryocytic progenitors may contribute to megakaryocytopenia.
Department of Pediatrics, Aflac Cancer Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Fang
F
Tan
Samit
S
Ghosh
Flaubert
F
Mbeunkui
Robert
R
Thomas
Joshua A
JA
Weiner
Solomon F
SF
Ofori-Acquah
D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000235:genetics*; D017209:Apoptosis; D019070:Cell Lineage; D050982:GATA1 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism
D020410:Activated-Leukocyte Cell Adhesion Molecule; D050982:GATA1 Transcription Factor; D011493:Protein Kinase C