The relevance of the hematopoietic niche for therapy resistance in acute myeloid leukemia

Abstract

The expansion of acute myeloid leukemia (AML) blasts not only suppresses normal hematopoiesis, but also alters the microenvironment. The interplay of different components of the bone marrow gives rise to altered metabolic states and activates signaling pathways which lead to resistance and impede effective therapy. Therefore, the underlying processes and mechanisms represent attractive therapeutic leverage points for overcoming therapy resistance in AML. Here, we briefly discuss resistance mechanisms based on cell interactions and secreted soluble factors in the hematopoietic niche and provide an overview of niche‐related therapeutic targets currently undergoing preclinical and clinical investigation which may help improve the outcome in AML therapy.

Autophagy and inflammasome molecular interplay and activation predict poor response to FLT3 inhibitors in patients with FLT3-ITD acute myeloid leukemia

“…In addition to genetic alterations, therapy opportunities might also lie in altered biological processes, a hallmark of AML onset and maintenance [3,4,15]. Biological processes such as autophagy and in ammasome are not only described to be functionally related in healthy contexts [16][17][18][19][20][21][22], but also to be altered in AML and positively affect the biological tness of AML cells in an isolated fashion [1,[23][24][25][26][27][28][29].…”