Exploiting epigenetically mediated changes: Acute myeloid leukemia, leukemia stem cells and the bone marrow microenvironment.

Exploiting epigenetically mediated changes: Acute myeloid leukemia, leukemia stem cells and the bone marrow microenvironment. Adv Cancer Res. 2019;141:213-253 Authors: Kogan AA, Lapidus RG, Baer MR, Rassool FV Abstract Acute myeloid leukemia (AML) derives from the clonal expansion of immature myeloid cells in the bone marrow, and results in the disruption of normal hematopoiesis and subsequent bone marrow failure. The bone marrow microenvironment (BME) and its immune and other supporting cells are regarded to facilitate the survival, differentiation and proliferation of leukemia stem cells (LSCs), which enables AML cells to persist and expand despite treatment. Recent studies have identified epigenetic modifications among AML cells and BME constituents in AML, and have shown that epigenetic therapy can potentially reprogram these alterations. In this review, we summarize the interactions between the BME and LSCs, and discuss changes in how the BME and immune cells interact with AML cells. After describing the epigenetic modifications seen across chromatin, DNA, the BME, and the immune microenvironment, we explore how demethylating agents may reprogram these pathological interactions, and potentially re-sensitize AML cells to treatment. PMID: 30691684 [PubMed - in process]
Source: Advances in Cancer Research - Category: Cancer & Oncology Authors: Tags: Adv Cancer Res Source Type: research