Flow cytometric detection of altered signaling in myelodysplastic syndrome and cytopenia

Multiparameter flow cytometric analysis allows for precise evaluation of growth factor stimulated intracellular signaling in distinct immunophenotype defined hematopoetic populations. Our analysis of intracellular phosphoprotein in response to major hematopoietic growth factors or cytokines showed several interesting findings. Although there was no characteristic signaling abnormality that was diagnostic for MDS, MDS cases were often associated with more signaling aberrancies involving more cellular populations. Higher than average response in the CD34(+)CD117(+) progenitor cells to Flt3 ligand and stem cell factor stimulation was frequently associated with high risk features or disease progression in MDS. Although preliminary results hint an adverse prognostic role of dysregulated FLT3 pathway in MDS cases, whether this observation adds independent prognostic value to the existing prognostic system needs to be further explored in future prospective studies.