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Landscape of Tumor Suppressor Mutations in Acute Myeloid Leukemia
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Location First: Targeting Acute Myeloid Leukemia Within Its Niche

1
Centro Ricerca M. Tettamanti, Department of Pediatrics, University of Milano-Bicocca, 20900 Monza, Italy
2
Department of Pediatrics, Pediatric Hematology-Oncology Unit, Fondazione MBBM/San Gerardo Hospital, 20900 Monza, Italy
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(5), 1513; https://doi.org/10.3390/jcm9051513
Received: 19 April 2020 / Revised: 11 May 2020 / Accepted: 14 May 2020 / Published: 18 May 2020
(This article belongs to the Special Issue Advances in Acute Myeloid Leukemia)
Despite extensive research and development of new treatments, acute myeloid leukemia (AML)-backbone therapy has remained essentially unchanged over the last decades and is frequently associated with poor outcomes. Eradicating the leukemic stem cells (LSCs) is the ultimate challenge in the treatment of AML. Emerging evidence suggests that AML remodels the bone marrow (BM) niche into a leukemia-permissive microenvironment while suppressing normal hematopoiesis. The mechanism of stromal-mediated protection of leukemic cells in the BM is complex and involves many adhesion molecules, chemokines, and cytokines. Targeting these factors may represent a valuable approach to complement existing therapies and overcome microenvironment-mediated drug resistance. Some strategies for dislodging LSCs and leukemic blasts from their protective niche have already been tested in patients and are in different phases of the process of clinical development. Other strategies, such as targeting the stromal cells remodeling processes, remain at pre-clinical stages. Development of humanized xenograft mouse models, which overcome the mismatch between human leukemia cells and the mouse BM niche, is required to generate physiologically relevant, patient-specific human niches in mice that can be used to unravel the role of human AML microenvironment and to carry out preclinical studies for the development of new targeted therapies. View Full-Text
Keywords: acute myeloid leukemia (AML); leukemic stem cell (LSC); bone marrow stromal cells; bone marrow niche; targeted therapy acute myeloid leukemia (AML); leukemic stem cell (LSC); bone marrow stromal cells; bone marrow niche; targeted therapy
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Pievani, A.; Biondi, M.; Tomasoni, C.; Biondi, A.; Serafini, M. Location First: Targeting Acute Myeloid Leukemia Within Its Niche. J. Clin. Med. 2020, 9, 1513.

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