Investigation of the effect of belinostat on MCF-7 breast cancer stem cells via the Wnt, Notch, and Hedgehog signaling pathway.

Transient abnormal myelopoiesis (TAM) and myeloid leukemia associated with Down syndrome (ML of DS) have morphologically indistinguishable blasts. TAM usually presents and regresses within the first three months of life. In a subset of patients, myelopoiesis remains abnormal, and the persistence of elevated blasts after 6 months is considered ML of DS. Current tools including cytogenetics and flow cytometry fail to distinguish blasts of TAM that will regress from blasts of ML of DS. One gene expression profiling study suggested PRAME expression was significantly increased in ML of DS compared to TAM. To further investigate this finding, we studied PRAME protein expression by immunohistochemistry in cases of TAM and ML of DS. PRAME immunoreactivity was found in blasts, dysplastic megakaryocytes, and fibroblasts. Four cases of TAM and fourteen cases of ML of DS had interpretable staining, with PRAME cytoplasmic reactivity in megakaryoblasts. Of the four cases of TAM, two were positive for PRAME; of the two patients, one had follow-up demonstrating ML of DS and the other had fully regressing TAM. Of the fourteen cases of ML of DS, ten had at least a subset of cells with positive PRAME staining, while four were negative for PRAME. In summary, PRAME immunoreactivity in ML of DS is largely due to the non-blast components, while PRAME immunoreactivity in blasts of TAM is not restricted to cases that progress to ML of DS.