Figure 3.

Pathophysiology of AML in the bone marrow. The bone marrow is a tissue organized to protect cell proliferation. Under normal conditions (left), the multipotent hematopoietic stem cells (HSCs) will give rise to the myeloid and the lymphoid lineages. Myeloid lineage transcription factors regulate the expression of CSF1R, already present in macrophage precursors. The stromal environment is composed by osteoblasts, osteoclasts, adipocytes, macrophages, mesenchymal cells, and vessels that will allow this differentiation process to take place. When there is a dysregulation of proliferation and apoptosis in myeloid precursors, hematologic malignancies such as AML may appear. In AML (right), proliferation and survival rely on the bone marrow stromal cells signals. These signals are strongly mediated by the CSF1R which is expressed in certain cell types (shown in the figure), contributing to paracrine communication.