title: A systematic analysis of bone marrow cells by flow cytometry defines a specific phenotypic profile beyond GPI deficiency in paroxysmal nocturnal hemoglobinuria.
abstract: BACKGROUND
  Paroxysmal nocturnal hemoglobinuria (PNH) is a unique disorder caused by a PIG-A gene mutation in a stem cell clone. Its clinical picture can sometimes make challenging the distinction from other disorders, and especially from myelodysplastic syndromes (MDS), since both diseases correlate with cytopenias and morphological abnormalities of bone marrow (BM) cells. Recently, flow cytometry (FC) has been proposed to integrate the morphologic assessment of BM dysplasia, and thus to improve the diagnostics of MDS.
  
  
  METHODS
  In the present study, we have analyzed systematically FC data resulting from the study of BM cells from patients with PNH and MDS.
  
  
  RESULTS
  Our data demonstrated abnormalities in PNH beyond the deficiency of glycosylphosphatidylinositol-linked proteins and the application of a systematic approach allowed us to separate effectively MDS and PNH in a cluster analysis and to highlight disease-specific abnormalities. Indeed, the parallel evaluation of some key parameters, i.e. patterns of expression of CD45 and CD10, provided information with practical diagnostic usefulness in the distinction between PNH and MDS. Moreover, the hypo-expression of CD36 that we observed on monocytes might be related to the thrombotic tendency in PNH.
  
  
  CONCLUSIONS
  We investigated systematically the phenotypic profile of BM cells from patients with PNH; our data provide useful antigenic patterns to solve between PNH and MDS, sometimes morphologically overlapping. Moreover, some PNH-related phenotypic changes might be involved in the physiopathology of the disease and further studies addressing this issue are warranted.
authors.affiliation: Unità Funzionale di Ematologia, Università degli Studi, AOU Careggi, Florence, Italy. francesco.mannelli@unifi.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Mannelli
authors.forename: Sara
authors.initials: S
authors.lastname: Bencini
authors.forename: Benedetta
authors.initials: B
authors.lastname: Peruzzi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cutini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sanna
authors.forename: Matteo
authors.initials: M
authors.lastname: Benelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Magi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Gianfaldoni
authors.forename: Giada
authors.initials: G
authors.lastname: Rotunno
authors.forename: Valentina
authors.initials: V
authors.lastname: Carrai
authors.forename: Anna Maria Grazia
authors.initials: AM
authors.lastname: Gelli
authors.forename: Veronica
authors.initials: V
authors.lastname: Valle
authors.forename: Valeria
authors.initials: V
authors.lastname: Santini
authors.forename: Rosario
authors.initials: R
authors.lastname: Notaro
authors.forename: Lucio
authors.initials: L
authors.lastname: Luzzatto
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology*; D018955:CD36 Antigens / Q000096:biosynthesis; D018958:CD55 Antigens / Q000235:genetics / Q000276:immunology; D018957:CD59 Antigens / Q000235:genetics / Q000276:immunology; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols / Q000172:deficiency; D006457:Hemoglobinuria, Paroxysmal / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D059785:Karyotype; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis*; D015260:Neprilysin / Q000096:biosynthesis; D010641:Phenotype; D012640:Seizures; D055815:Young Adult
chemical_list: D018955:CD36 Antigens; D018958:CD55 Antigens; D018957:CD59 Antigens; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein; D017493:Leukocyte Common Antigens; D015260:Neprilysin