Fig. 5: Proposed working model.

Distinct differentiation trajectories characterize the HSPC compartment in healthy adults (left) and MDS patients at the time of diagnosis (middle) and progression (right). MDS can be classified as one of two immunophenotypically distinct groups, CMP-pattern MDS or GMP-pattern MDS, based on the frequency of CMPs or GMPs, respectively, in the MyHPC compartment. In each group, MDS stem cells in distinct differentiation states (LT-HSCs in CMP-pattern MDS or LMPPs in GMP-pattern MDS) maintain the disease during HMA-based therapy and expand at progression. Specific survival pathways are selectively activated in each MDS stem cell type at BP and drive disease transformation. Er, erythrocyte; Gran, granulocyte; Mk, megakaryocyte; Mono/macro, monocyte/macrophage.