Research Topic

Microenvironment and Therapy-Resistance in Leukemias

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About this Research Topic

Relapsed and refractory B-cell acute lymphoblastic leukemia (ALL) remains difficult to treat, despite the advances in upfront therapy, improved survival for de novo ALL or growing immunotherapeutic interest using engineered CAR T-cells or monoclonal antibodies. Acute myeloid leukemia (AML) has a poor overall ...

Relapsed and refractory B-cell acute lymphoblastic leukemia (ALL) remains difficult to treat, despite the advances in upfront therapy, improved survival for de novo ALL or growing immunotherapeutic interest using engineered CAR T-cells or monoclonal antibodies. Acute myeloid leukemia (AML) has a poor overall survival of 40-60% in children and adults. Increasing characterization of the genetic landscape has not led- with a few exceptions- to many new therapeutic options.

It is well known that the microenvironment can mediate resistance of ALL and AML cells to chemotherapy. However, very few drugs are FDA approved to target this niche. Discovery of new targets in the microenvironment of leukemia and a precise understanding of the underlying mechanisms of microenvironment-mediated therapy resistance are critical for new drug designs. While the bone marrow niche of therapy-resistant leukemia cells has been described to consist of cellular and soluble components, the knowledge of key players in the tumor microenvironment is expanding, adding more pieces to the puzzle. The microenvironment niche consists of endothelial, osteoblastic and stromal niches, but also the nervous system and cellular components including adipocytes and immune cells that have been shown to contribute to therapy resistance. Soluble factors include cytokines, chemokines, growth factors, exosomes, and miRNA; recent studies have shown a direct transfer of mitochondria from the stroma to tumor cells. Cell-cell and cell-matrix adhesion molecules, galectins and associated signaling pathways warrant consideration. Further niche characteristics include hypoxia, altered metabolism, and senescence. Imaging studies and genomic analysis may add new information to our understanding of the niches. Understanding the contribution of the tumor microenvironment in CART cell relapse of leukemia cells may be important for advancing immunotherapy further.

This Research Topic will focus on acute lymphoblastic and myeloid leukemia and the contribution of the microenvironment to therapeutic resistance leading to relapse of the disease. We welcome submissions focusing on these key cellular, non-cellular, molecular and therapeutic aspects of the microenvironment of ALL and AML to understand and target the microenvironment of therapy-resistant (chemotherapy and immunotherapy) leukemia.


Topic editor Marina Konopleva has received consultancy fees from Abbvie, Genentech, F. Hoffman La-Roche, Cellectis, and Stemline Therapeutics; research funding from Eli Lilly, Ablynx, Calithera, Threshold Pharmaceuticals, Flexus Biosciences, Novartis, and Agios; honoraria from Amgen; and has stock options from Reata Pharmaceutical. All other topic editors declare no competing interests with regards to the Research Topic subject.


Keywords: Microenvironment, Leukemia, Drug resistance, Immunotherapy resistance, Cell-adhesion-mediated resistance


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