Figure 1.

Leukaemogenesis and remodelling of the bone marrow niche by leukaemic cells. (A) Oncogenic transformation of haematopoietic cells into leukaemic cells can be initiated by cell-intrinsic genetic alterations in surrounding bone marrow niche cells. (B) During leukaemogenesis, malignant cells can hijack the mechanisms of homing used by healthy haematopoietic stem cells and directly compete with haematopoietic stem cells for endosteal adhesion, resulting in transformation of the healthy niche microenvironment into a tumour-supportive niche. Furthermore, leukaemic cells are capable of remodelling the (C) central vascular and (D) endosteal vascular niche into leukaemia-supportive microenvironments that favour leukaemia cell survival and expansion, with hostility towards physiological haematopoiesis. (E) Leukaemic cells can promote remodelling of bone compartments by directly influencing the differentiation and/or function of osteoblasts and osteoclasts, leading to severely impaired bone homeostasis.