Peripheral blood MDS score: a new flow cytometric tool for the diagnosis of myelodysplastic syndromes.
BACKGROUND
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders diagnosed using morphologic and clinical findings supported by cytogenetics. Because abnormalities may be subtle, diagnosis using these approaches can be challenging. Flow cytometric (FCM) approaches have been described; however the value of bone marrow immunophenotyping in MDS remains unclear due to the variability in detected abnormalities. We sought to refine the FCM approach by using peripheral blood (PB) to create a clinically useful tool for the diagnosis of MDS.


METHODS
PB from 15 patients with MDS was analyzed by multiparametric flow cytometry using an extensive panel of monoclonal antibodies. Patterns of neutrophil antigen expression were compared with those of normal controls (n = 16) to establish light scatter and/or immunophenotypic abnormalities that correlated with MDS. A scoring algorithm was developed and validated prospectively on a blinded patient set.


RESULTS
PB neutrophils from patients with MDS had lower side scatter and higher expression of CD66 and CD11a than did controls. Some MDS PB neutrophils demonstrated abnormal CD116 and CD10 expression. Because none of these abnormalities proved consistently diagnostic, we sought to increase the power of the assay by devising a scoring system to allow the association of multiple abnormalities and account for phenotypic variations. The PB MDS score differentiated patients with MDS from controls (P < 0.0001) in the test set. In a prospective validation, the PB MDS score successfully identified patients with MDS (sensitivity 73%, specificity 90%).


CONCLUSIONS
FCM analysis of side scatter and only four additional immunophenotypic parameters of PB neutrophils using the PB MDS score proved more sensitive than standard laboratory approaches and may provide an additional, more reliable diagnostic tool in the identification of MDS.
Cherian
Sindhu
S
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. cherians@uphs.upenn.edu
Moore
Jonni
J
Bantly
Andrew
A
Vergilio
Jo-Anne
JA
Klein
Peter
P
Luger
Selina
S
Bagg
Adam
A
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D040881:CD11a Antigen / Q000032:analysis; D015815:Cell Adhesion Molecules; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000378:metabolism; D009504:Neutrophils / Q000737:chemistry / Q000473:pathology; D012680:Sensitivity and Specificity
D015703:Antigens, CD; D000943:Antigens, Differentiation; D040881:CD11a Antigen; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D017493:Leukocyte Common Antigens