title: Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group.
abstract: Current recommendations for diagnosing myelodysplastic syndromes endorse flow cytometry as an informative tool. Most flow cytometry protocols focus on the analysis of progenitor cells and the evaluation of the maturing myelomonocytic lineage. However, one of the most frequently observed features of myelodysplastic syndromes is anemia, which may be associated with dyserythropoiesis. Therefore, analysis of changes in flow cytometry features of nucleated erythroid cells may complement current flow cytometry tools. The multicenter study within the IMDSFlow Working Group, reported herein, focused on defining flow cytometry parameters that enable discrimination of dyserythropoiesis associated with myelodysplastic syndromes from non-clonal cytopenias. Data from a learning cohort were compared between myelodysplasia and controls, and results were validated in a separate cohort. The learning cohort comprised 245 myelodysplasia cases, 290 pathological, and 142 normal controls; the validation cohort comprised 129 myelodysplasia cases, 153 pathological, and 49 normal controls. Multivariate logistic regression analysis performed in the learning cohort revealed that analysis of expression of CD36 and CD71 (expressed as coefficient of variation), in combination with CD71 fluorescence intensity and the percentage of CD117+erythroid progenitors provided the best discrimination between myelodysplastic syndromes and non-clonal cytopenias (specificity 90%; 95% confidence interval: 84-94%). The high specificity of this marker set was confirmed in the validation cohort (92%; 95% confidence interval: 86-97%). This erythroid flow cytometry marker combination may improve the evaluation of cytopenic cases with suspected myelodysplasia, particularly when combined with flow cytometry assessment of the myelomonocytic lineage.
authors.affiliation: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, The Netherlands tm.westers@VUmc.nl.
authors.forename: Theresia M
authors.initials: TM
authors.lastname: Westers
authors.affiliation: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, The Netherlands.
authors.forename: Eline M P
authors.initials: EM
authors.lastname: Cremers
authors.affiliation: Department of Internal Medicine, Universitätsklinikum "Carl-Gustav-Carus", Dresden, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Oelschlaegel
authors.affiliation: Department of Haematology, University Hospitals NHS Foundation Trust, Bristol, UK.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Johansson
authors.affiliation: First Medical Department, Elisabethinen Hospital, Linz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Bettelheim
authors.affiliation: Servicio Central de Citometría (NUCLEUS) and Department of Medicine, Centro de Investigación del Cáncer, Instituto de Biologia Celular y Molecular del Cáncer, (CSIC/USAL and IBSAL), Universidad de Salamanca, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Matarraz
authors.affiliation: Servicio Central de Citometría (NUCLEUS) and Department of Medicine, Centro de Investigación del Cáncer, Instituto de Biologia Celular y Molecular del Cáncer, (CSIC/USAL and IBSAL), Universidad de Salamanca, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Isala Clinics, Zwolle, The Netherlands.
authors.forename: Bijan
authors.initials: B
authors.lastname: Moshaver
authors.affiliation: HematoLogics, Inc., Seattle, WA, USA.
authors.forename: Lisa Eidenschink
authors.initials: LE
authors.lastname: Brodersen
authors.affiliation: HematoLogics, Inc., Seattle, WA, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Loken
authors.affiliation: HematoLogics, Inc., Seattle, WA, USA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Wells
authors.affiliation: Department of Hematology, Hospital Universitario de Guadalajara, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Subirá
authors.affiliation: HMDS, St. James's University Hospital, Leeds, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Cullen
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Jeroen G
authors.initials: JG
authors.lastname: Te Marvelde
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Vincent H J
authors.initials: VH
authors.lastname: van der Velden
authors.affiliation: Department of Laboratory Medicine - Laboratory for Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Frank W M B
authors.initials: FW
authors.lastname: Preijers
authors.affiliation: Department of Hematology and Oncology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan.
authors.forename: Sung-Chao
authors.initials: SC
authors.lastname: Chu
authors.affiliation: Laboratoire d'Hématologie, CHU Dupuytren, Limoges, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Feuillard
authors.affiliation: Laboratoire d'Hématologie, CHU Dupuytren, Limoges, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Guérin
authors.affiliation: Department of Immunology-Histocompatibility, Evangelismos Hospital, Athens, Greece.
authors.forename: Katherina
authors.initials: K
authors.lastname: Psarra
authors.affiliation: Department of Pathobiology and Laboratory Medicine, University of Toronto, University Health Network, Toronto General Hospital, ON, Canada.|Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Porwit
authors.affiliation: Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Leonie
authors.initials: L
authors.lastname: Saft
authors.affiliation: King's College Hospital, London, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Ireland
authors.affiliation: King's College Hospital, London, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Milne
authors.affiliation: Laboratoire d'Hématologie, CHU de Nantes, France.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Béné
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Birgit I
authors.initials: BI
authors.lastname: Witte
authors.affiliation: Department of Hematology and Oncology, Fondazione IRCCS Policlinico San Matteo, and University of Pavia, Italy.
authors.forename: Matteo G
authors.initials: MG
authors.lastname: Della Porta
authors.affiliation: MLL Munich Leukemia Laboratory, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.affiliation: Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, The Netherlands.
authors.forename: Arjan A
authors.initials: AA
authors.lastname: van de Loosdrecht
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000378:metabolism; D016022:Case-Control Studies; D041905:Erythroid Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers