β-thalassemia hematopoietic stem cells (HSCs) appear to be more committed toward erythroid differentiation, according to a study presented at the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.
The study, which was presented by Maria Rosa Lidonnici, PhD, of the IRCCS San Raffaele Scientific Institute in Italy, aimed to investigate whether bone marrow overstimulation affects hematopoietic differentiation in β-thalassemia.
“…Since [β-thalassemia] is an erythropoietic disease, we want to use this disease as disease model to study ‘erythroid branching’ in the hematopoietic hierarchy,” said Dr Lidonnici.
Dr Lidonnici and colleagues conducted immunophenotype and functional analysis of the lineage commitment of primitive HSCs/multipotent progenitor (MPP) cells in patients with β-thalassemia and cells from healthy donors, which were used as controls.
The investigators found an increased proportion of MPPs in β-thalassemia patients compared to controls in the primitive compartment. In subset1 (defined as CLEC9AhighCD34low), which the investigators noted had multilineage potential, β-thalassemia HSC/MPPs were able to produce more erythroid colonies than the control cells, demonstrating enhanced erythroid potential.
When assessing progenitor (CD34+ CD38+) cells, the investigators quantified the new myeloid (CD71–BAH1-/+) and erythroid (CD71+ BAH1-/+) subsets and found a reduced fraction of the erythroid subset in β-thalassemia samples relative to control samples. This led the team to hypothesize that the erythroid-enriched subsets differentiate more rapidly due to higher sensitivity to positive regulators of erythropoiesis.
To characterize the transcriptional networks regulating hematopoiesis in β-thalassemia, the team conducted RNA sequencing on sorted hematopoietic subpopulations from the bone marrow in both groups.
The gene enrichment analysis of the RNA sequencing data revealed that compared with the control samples the β-thalassemia HSC/MPP samples had a lack of genes/pathways related to stemness and quiescence. They also noted that some genes involved in that erythropoiesis regulation were overrepresented in the β-thalassemia across the hematopoietic cascade.
“In conclusion, [β-thalassemia] primitive cells are more committed towards the erythroid branching,” said Dr Lidonnici. The authors speculated that this tendency is likely due to chronic bone marrow stimulation.
Lidonnici MR, Chianella G, Tiboni F, et al. Hematopoietic stem cells with erythroid signature in beta-thalassemia. Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S299.