Thymic Stromal Lymphopoeitin from Bone Marrow Niches Supports Acute Lymphoblastic Leukemia Cancer Progression
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Abstract
Thymic stromal lymphopoietin (TSLP) is an interleukin (IL), a cytokine produced and released
from white blood cells, that is involved in the inflammatory process and cancer (Ziegler et al.,
2013). Originally discovered in thymic stromal cells, mouse and human TSLP proteins share
significant functional homology. Since its identification, TSLP was also found to be produced in
keratinocytes, epithelial, and stromal cells and reported to function as a growth factor that can
promote B‐cell development (Ziegler et al., 2013). Moreover, TSLP signaling has been found to
increase the risk of acute lymphoblastic leukemia (ALL), a cancer effecting blood lymphocytes.
Specifically, TSLP is thought to enhance the survival of these leukemic cells (Chen et al., 2012).
The ALL phenotype would most likely be found in clusters or “niches” of the bone marrow (BM),
where leukemic cells are created. The identification of the presence of leukemic niches is
therefore the first step towards developing the suspected link between ALL and TSLP.
Since human TSLP and mouse TSLP share significant functional homology, mouse models have
been used to accurately predict the behavior of TSLP in humans. Therefore, the next step
towards targeting TSLP signaling in ALL would be to determine whether mouse lymphocytes
secrete TSLP. This can be accomplished by measuring relative gene expression levels of Tslp in
mouse organs that are lymphocyte‐rich. Along with mouse thymus, mouse bone marrow (BM)
showed comparable and significant levels of relative gene expression. This data confirms that
TSLP is secreted by cells in the mouse femur BM. The implications to this conclusion may
suggest that mouse and human TSLP signaling in BM is involved in the progression of ALL.