Clonal architecture of del(5q) myelodysplastic syndromes: aberrant CD5 or CD7 expression within the myeloid progenitor compartment defines a subset with high clonal burden

Myelodysplastic syndromes (MDSs) represent a heterogeneous hematopoietic stem cell disorder.1 A precise estimation of the prognosis within the various MDS subgroups is essential for tailored therapeutic decisions. Especially, MDS patients with an isolated deletion of the long arm of chromosome 5 (del(5q)) represent a distinct subgroup regarding clinical outcome with a favorable prognosis in the majority of cases.2 Furthermore, they present with characteristic cytomorphological features, such as hypolobated megakaryocytes, macrocytic anemia and a normal or increased peripheral platelet count.3 Recently, flow cytometry (FCM) has been shown to serve as a valuable additional diagnostic and prognostic tool, especially to separate between unilineage and multilineage dysplasia.4, 5 Besides, it is known that abnormal antigen expression on myeloid progenitor cells (myPCs) is associated with a poor outcome.6, 7 In fact, aberrant CD7 expression on myPC of anemic lower-risk MDS patients predicts for a significantly lower response rate to erythropoiesis-stimulating agent (ESA) therapy irrespective of comparable other clinical predictive markers (erythropoietin level, transfusion burden).8 The pathophysiological background for this observation is still unknown. Notably, it has not been shown so far whether these distinct immunophenotypic characteristics correlate with presence and extent of clonal hematopoiesis, which in turn might not be responsive to growth factor stimulation. Therefore, in this study we separated different hematopoietic cell compartments of del(5q) MDS patients by fluorescence-activated cell sorting (FACS) and quantified the respective distribution of clonal burden with interphase fluorescence in situ hybridization (iFISH).