Abstract
Stem cell antigen-1 (Ly6a/Sca-1) is a gene that is expressed in activated lymphocytes, hematopoietic stem cells and stem cells of a variety of tissues in mice. Despite decades of study its functions remain poorly defined. These studies explored the impact of expression of this stem cell associated gene in acute lymphoid leukemia. Higher levels of Ly6a/Sca-1 expression led to more aggressive leukemia growth in vivo and earlier death of hosts. Leukemias expressing higher levels of Ly6a/Sca-1 exhibited higher levels of matrix metalloproteinases. The results suggest the hypothesis that the more aggressive behavior of Ly6a/Sca-1 expressing leukemias is due at least in part to greater capacity to degrade microenvironmental stroma and invade tissues.
Highlights
We recently discovered that acute lymphoid leukemia cells increase expression of some genes in vivo in the allogeneic environment, many of which are related to immune function [1]
Growth in vivo was examined and we observed that 0animals that were challenged with the leukemia that had higher levels of Ly6a/stem cell antigen-1 (Sca-1) expression exhibited shorter survival compared to those challenged with leukemia cells with low Ly6a/Sca-1 expression (Figure 1C)
Earlier work in our experimental system suggested the hypothesis that increased expression of Ly6a/Sca-1 would confer an advantage in vivo for leukemia cells [1]
Summary
We recently discovered that acute lymphoid leukemia cells increase expression of some genes in vivo in the allogeneic environment, many of which are related to immune function [1]. One of these genes is lymphocyte antigen 6 locus A, Ly6a, originally discovered in the 1970s in activated lymphocytes [2,3]. The exact functions of Ly6a/Sca-1 remain unknown. It is a glycosylphosphatidylinositol (GPI)-anchored protein present in a complex cell-surface lipid raft and likely functions as a coregulator of lipid raft mediated cell signaling [9,10]. An excellent review was published in 2007 that highlights the molecule’s roles in immune function, hematopoiesis and stem cell biology [14]
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