The immunophenotype of different immature, myeloid and B-cell lineage-committed CD34⁺ hematopoietic cells allows discrimination between normal/reactive and myelodysplastic syndrome precursors

Abstract

Occurrence of phenotypic abnormalities in CD34⁺ hematopoietic progenitor and precursor cells (HPC) and their major B-cell and nonlymphoid compartments has been frequently reported in myelodysplastic syndromes (MDS). Here, we analyze for the first time the numerical and phenotypic abnormalities of different maturation-associated subsets of bone marrow (BM) CD34⁺ HPC from 50 newly diagnosed MDS patients in comparison to normal/reactive BM (n=29). Our results confirm the existence of heterogeneously altered phenotypes among CD34⁺ HPC from MDS and indicate that such variability depends both on the relative distribution of the different subsets of CD34⁺ HPC committed into the different myeloid and B-lymphoid compartments, and their immunophenotype (for example, higher reactivity for CD117 and CD13 and lower expression of CyMPO, CD64 and CD65 on CD34⁺ immature and neutrophil precursors), a clear association existing between the accumulation of CD34⁺ HPC and that of immature CD34⁺ HPC. Interestingly, expansion of erythroid- and neutrophil-lineage CD34⁺ cells is detected in low-grade MDS at the expense of CD34⁺ plasmacytoid dendritic cell and B-cell precursors, while expansion of immature CD34⁺ precursors occurs in high-grade MDS. On the basis of the number and severity of the phenotypic abnormalities detected, a scoring system is proposed that efficiently discriminates between normal/reactive and MDS CD34⁺ HPC, the mean score significantly increasing from low- to high-grade MDS.