A new study shows that leukemic stem cells that propagate myeloproliferative disorders can harness stromal cells in the bone marrow niche to favor their own function and induce fibrosis while impairing normal hematopoiesis (Cell Stem Cell, 13, 285–299 ).

Koen Schepers et al. showed that endosteal stromal cells, found at the bone surface of the bone marrow, can give rise to osteoblastic cells, which can then maintain hematopoietic stem cells. Using a mouse model of human chronic myelogenous leukemia, the authors showed that disease development in these mice resulted in expansion of osteoblastic cells and bone marrow fibrosis, which is often found in humans with myeloproliferative disorders. Cell–cell interactions and factors released by leukemic stem cells induced stromal cells to overproduce cells of the osteoblastic lineage, but these cells had an inflammatory phenotype that supported leukemic hematopoiesis and myelofibrosis at the expense of normal hematopoietic activity. The authors also investigated the genes involved in this process in myeloproliferative osteoblastic cells. Compared with control osteoblastic cells, they detected an increased expression of genes driving extracellular matrix organization and inflammatory responses, which are probably involved in tissue remodeling, and a downregulation of genes involved in maintaining normal hematopoiesis.

Although future studies should address the exact molecular underpinnings of these findings and their relevance in people with myeloproliferative disease, the results further our understanding of how leukemic cells exploit the bone marrow niche to reinforce leukemic growth at the expense of normal hematopoiesis.