Identification of distinct prognostic subgroups in low- and intermediate-1–risk myelodysplastic syndromes by flow cytometry

Abstract

The World Health Organization (WHO) classification contributes to refined classification and prognostication of myelodysplastic syndromes (MDSs). Flow cytometry might add significantly to diagnostic and prognostic criteria. Our analysis of bone marrow samples from 50 patients with MDS showed aberrant expression of differentiation antigens in the myelomonocytic lineage. This also accounted for refractory anemia (RA) with or without ringed sideroblasts (RS), indicating multilineage dysplasia. In 38% of patients, CD34 ؉ myeloid blasts expressed CD5, CD7, or CD56. Flow cytometry data were translated into a numerical MDS flow-score. Flow-scores increased significantly from RA with or without RS, refractory cytopenia with multilineage dysplasia (RCMD) with or without RS up to refractory anemia with excess of blasts-1 (RAEB-1) and RAEB-2. No significant differences were observed between WHO cytogenetic subgroups. Flow-scores were highly heterogeneous within International Prognostic Scoring System (IPSS) subgroups. Patients in progression to advanced MDS or acute myeloid leukemia had a significantly higher flow-score compared with non-transfusion-dependent patients. In 60% of patients with transfusion dependency or progressive disease, myeloid blasts expressed CD7 or CD56, in contrast to only 9% of non-transfusiondependent patients. Moreover, all patients with pure RA with or without RS with aberrant myeloid blasts showed an adverse clinical course. In conclusion, flow cytometry in MDS identified aberrancies in the myelomonocytic lineage not otherwise determined by cytomorphology. In addition, flow cytometry identified patients at risk for transfusion dependency and/or progressive disease independent of known risk groups, which might have impact on treatment decisions and the prognostic scoring system in the near future.

Clinical utility of multiparameter flow cytometry in the diagnosis of 1013 patients with suspected myelodysplastic syndrome

“…MFC is capable of identifying dysplastic features in BM samples and, thus, was supposed to be added to the diagnostic workup in patients who have suspected MDS. [13][14][15][16]32,34 In the current study, several aspects regarding the specificity and sensitivity of MFC for diagnosing MDS have been elucidated in agreement with previous studies. 15,16 In the current series and in the data reported by van de Loosdrecht et al, 16 this also is true for the identification of dysplastic features in cell lineages that were not rated dysplastic by CM alone.…”

“…This was reported previously by van de Loosdrecht et al 16 and was reproduced here by the identification of an aberrant antigen expression in granulocytes in patients who had no dysgranulopoiesis according to the CM results.…”

“…[13][14][15][16] These findings have been described in MDS and do not occur or occur only infrequently in patients who have cytopenias that are not considered MDS. The objective of the current study was to estimate the potential diagnostic value of MFC.…”

“…Although the majority of previous reports focused on patients with proven MDS and, in part, added control samples from patients who clearly did not have a malignancy, [13][14][15][16] in the current study, a large series of 1013 patients with suspected MDS was the focus of our analyses. None of these patients had undergone a prior proof or rule out of MDS.…”

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

“…When the morphological dysplastic features are mild or even absent and PB cytopenias are persistent the diagnosis is termed idiopathic cytopenias of undetermined significance (ICUS) (Valent et al , 2012; Bejar & Steensma, 2014). Evaluating myelodysplastic features using flow cytometry is a growing field of interest and highly sensitive multicolour immunophenotypic profiling and accompanying scoring systems have proven useful in MDS, both in diagnostic and prognostic terms (Ogata et al , 2006; van de Loosdrecht et al , 2008). …”