title: Flow cytometric detection of altered signaling in myelodysplastic syndrome and cytopenia.
abstract: 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.
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Feinberg 7-209A, 251 E. Huron Street, Chicago, IL 60611, USA. Electronic address: j-gao@northwestern.edu.
authors.forename: Juehua
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Feinberg 7-209A, 251 E. Huron Street, Chicago, IL 60611, USA.
authors.forename: Suchitra
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Feinberg 7-209A, 251 E. Huron Street, Chicago, IL 60611, USA.
authors.forename: Navin
authors.initials: N
authors.lastname: Pai
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Feinberg 7-209A, 251 E. Huron Street, Chicago, IL 60611, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Johnson
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Feinberg 7-209A, 251 E. Huron Street, Chicago, IL 60611, USA.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Feinberg 7-209A, 251 E. Huron Street, Chicago, IL 60611, USA.
authors.forename: LoAnn
authors.initials: L
authors.lastname: Peterson
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Feinberg 7-209A, 251 E. Huron Street, Chicago, IL 60611, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Goolsby
mesh_terms: D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods*; D006410:Hematopoiesis / Q000235:genetics*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D020935:MAP Kinase Signaling System; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D010198:Pancytopenia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D010750:Phosphoproteins / Q000032:analysis*; D050799:STAT5 Transcription Factor / Q000502:physiology; D015398:Signal Transduction; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D010750:Phosphoproteins; D050799:STAT5 Transcription Factor; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Flow cytometry; Growth factor; Myelodysplatic syndrome; Phosphoprotein