Abstract
BackgroundActivated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells. However, its role in hematopoietic differentiation has not previously been defined.ResultsIn 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.ConclusionsThere 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.
Highlights
Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells
Antibodies against various adhesion molecules including VLA-4 and VCAM-1 inhibit the ability of hematopoietic stem cells to populate the bone marrow of irradiated mice [5], and gene knock-out studies of integrins have shown their critical role in homing and colonization of late-stage primary hematopoietic organs such as the embryonic liver [6,7]
This expression pattern was confirmed at the protein level as none of the erythromegakaryocytic progenitor cell lines (K562, MEG-01) expressed ALCAM, while ALCAM protein was abundant in THP-1 monocytes (Figure 1B)
Summary
Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells. Hematopoiesis is controlled by interactions between hematopoietic stem cells and their microenvironment These interactions influence retention of stem cells in specific niches, and stem and progenitor cell expansion, lineage divergence and differentiation [1]. N-cadherin expression has been implicated in retention of hematopoietic stem cells in the bone marrow niche [8,9,10] this claim is not supported by other studies [11]. In contrast to their role in homing, our understanding of adhesion molecule biology in lineage commitment and differentiation is poorly defined
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