RNA-seq in different hematopoietic stem and progenitor cell subpopulations of patients with chronic and progressed polycythemia vera and controls

Hematopoietic stem/multipotent progenitor cells (HSC/MPPs, referred to as HSCs) can differentiate into functionally divergent cell lineages including common myeloid progenitors (CMPs), megakaryocyte-erythrocyte progenitors (MEPs) or granulocyte-macrophage progenitors (GMPs). When this stem cell differentiation process is altered, abnormal (pre)leukemic stem cell subpopulations may form, eventually resulting in clonal hematopoiesis and in the onset of chronic or acute leukemias such as for example polycythemia vera (PV) or acute myeloid leukemia (AML). To understand the molecular and biochemical changes underlying trilineage hyperproliferation in PV and the process of progression to post-PV myelofibroses (post-PV MF) or post-PV acute myeloid leukemia (post-PV AML), highly refined analyses of PV stem and progenitor cells are required. We performed transcriptomics and proteomics analyses in hematopoietic stem and progenitor cells of patients with chronic and progressed PV as well as controls to identify key molecular changes in these cell subpopulations for disease manifestation and progression. Unbiased RNA-seq analysis was performed in HSC/MPPs, CMP/MEPs, CMP, MEPs and GMPs of 18 patients with chronic and progressed PV and 21 controls.