title: Phenotypic abnormalities strongly reflect genotype in patients with unexplained cytopenias.
abstract: BACKGROUND
  In patients with unexplained cytopenias, abnormal karyotyping studies can be found with inconclusive light microscopic findings. Multidimensional flow cytometry (FCM) can identify myelomonocytic cells with aberrant phenotypes often not seen by standard morphology.
  
  
  METHODS
  In 431 patients presenting with unexplained cytopenia(s) FCM results were compared to abnormal karyotyping and FISH results recognized as associated with myelodysplastic syndrome (MDS) in the 2008 WHO classification, to assess the degree of and types of phenotypic abnormalities observed using a previously reported flow cytometric scoring system (FCSS). Fluorescence activated cell sorting was also used to identify subpopulations of abnormal maturing myelomonocytic cells that carry the genotypic abnormality.
  
  
  RESULTS
  For marrows with complex (three or more karyotypic abnormalities), two abnormalities, isolated chromosome seven anomalies, del(5q) or del(13q), 100% of cases were positive when using a FCSS cutoff of ≥ 2. Trisomy 8, del(20 q), and minus Y had flow scores ≥ 2 in 72, 60, and 18%, respectively, but in some cases the flow score was high, indicating myeloid dysplasia. Most patients (16/22) with high myeloid progenitor cells (MyPC) (> 20%) also exhibited maturing myeloid cell abnormalities by FCM. Morphology was negative in the maturing myeloid cells in many cases with phenotypically abnormal myeloid cells.
  
  
  CONCLUSIONS
  The high correlation between genotypic and phenotypic abnormalities suggests a possible increased utility of flow cytometry in the diagnosis of patients with unexplained cytopenias and may be useful in future clinical studies and in the classification by the WHO, using the FCSS rather than simple counting of flow cytometric abnormalities.
authors.affiliation: Hematologics, Seattle, Washington, 98121, USA. jevon@hematologics.com
authors.forename: Jevon A
authors.initials: JA
authors.lastname: Cutler
authors.forename: Denise A
authors.initials: DA
authors.lastname: Wells
authors.forename: Arjan A
authors.initials: AA
authors.lastname: van de Loosdrecht
authors.forename: Monica E
authors.initials: ME
authors.lastname: de Baca
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kalnoski
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Zehentner
authors.forename: Lisa
authors.initials: L
authors.lastname: Eidenschink
authors.forename: Keely M
authors.initials: KM
authors.lastname: Ghirardelli
authors.forename: Julie Sanford
authors.initials: JS
authors.lastname: Biggerstaff
authors.forename: Michael R
authors.initials: MR
authors.lastname: Loken
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D023461:Myeloid Progenitor Cells / Q000473:pathology*; D010641:Phenotype; D055815:Young Adult