Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis

Figure 4

Proposal of a natural history of hematopoietic and stromal cell interactions in bone marrow from PMF patients. The highly inflammed bone marrow environment in PMF is compared to being hit by a “storm” of cytokines [12] (0). (1) This inflammatory environment could involve hematopoietic stem cells (HSCs) and/or mesenchymal stromal cells (MSCs). (2) Clonal events (that would be favored/driven by inflammation (?) [13]) would give rise to clonal hematopoietic cell(s) which will further differentiate into megakaryocytes and monocytes and produce large amount of inflammatory cytokines. (3) These cytokines would modify the bone marrow microenvironment, leading (4) to a permanent impairment of MSCs and a deterioration of the hematopoietic niche. (5) Impaired MSCs would influence malignant hematopoietic cells in an altered crosstalk and over time, MSCs would become inflammatory imprinted. (5) As a result of treatment, the number of malignant hematopoietic cells will reduce. However, the influence of inflammatory imprinted MSCs that would have acquired inherited impaired functions will continue. Unless treated, disease MSCs may continue interacting with HSC and contribute to relapse of the disease (6).