Emerging Bone Marrow Microenvironment-Driven Mechanisms of Drug Resistance in Acute Myeloid Leukemia: Tangle or Chance?

Acute myeloid leukemia (AML) has been considered for a long time exclusively driven by critical mutations in hematopoietic stem cells. Recently, the contribution of further players, such as stromal and immune bone marrow (BM) microenvironment components, to AML onset and progression has been pointed...

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Autores principales:	Marilena Ciciarello, Giulia Corradi, Dorian Forte, Michele Cavo, Antonio Curti
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hematology chemotherapy resistance bone marrow microenvironment mesenchymal stromal cells immune microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f5a7acbfc1d847669fca4b91a91523bf
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spelling	oai:doaj.org-article:f5a7acbfc1d847669fca4b91a91523bf2021-11-11T15:28:16ZEmerging Bone Marrow Microenvironment-Driven Mechanisms of Drug Resistance in Acute Myeloid Leukemia: Tangle or Chance?10.3390/cancers132153192072-6694https://doaj.org/article/f5a7acbfc1d847669fca4b91a91523bf2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5319https://doaj.org/toc/2072-6694Acute myeloid leukemia (AML) has been considered for a long time exclusively driven by critical mutations in hematopoietic stem cells. Recently, the contribution of further players, such as stromal and immune bone marrow (BM) microenvironment components, to AML onset and progression has been pointed out. In particular, mesenchymal stromal cells (MSCs) steadily remodel the leukemic niche, not only favoring leukemic cell growth and development but also tuning their responsiveness to treatments. The list of mechanisms driven by MSCs to promote a leukemia drug-resistant phenotype has progressively expanded. Moreover, the relative proportion and the activation status of immune cells in the BM leukemic microenvironment may vary by influencing their reactivity against leukemic cells. In that, the capacity of the stroma to re-program immune cells, thus promoting and/or hampering therapeutic efficacy, is emerging as a crucial aspect in AML biology, adding an extra layer of complexity. Current treatments for AML have mainly focused on eradicating leukemia cells, with little consideration for the leukemia-damaged BM niche. Increasing evidence on the contribution of stromal and immune cells in response to therapy underscores the need to hold the mutual interplay, which takes place in the BM. A careful dissection of these interactions will help provide novel applications for drugs already under experimentation and open a wide array of opportunities for new drug discovery.Marilena CiciarelloGiulia CorradiDorian ForteMichele CavoAntonio CurtiMDPI AGarticlehematologychemotherapy resistancebone marrow microenvironmentmesenchymal stromal cellsimmune microenvironmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5319, p 5319 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hematology chemotherapy resistance bone marrow microenvironment mesenchymal stromal cells immune microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hematology chemotherapy resistance bone marrow microenvironment mesenchymal stromal cells immune microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Marilena Ciciarello Giulia Corradi Dorian Forte Michele Cavo Antonio Curti Emerging Bone Marrow Microenvironment-Driven Mechanisms of Drug Resistance in Acute Myeloid Leukemia: Tangle or Chance?
description	Acute myeloid leukemia (AML) has been considered for a long time exclusively driven by critical mutations in hematopoietic stem cells. Recently, the contribution of further players, such as stromal and immune bone marrow (BM) microenvironment components, to AML onset and progression has been pointed out. In particular, mesenchymal stromal cells (MSCs) steadily remodel the leukemic niche, not only favoring leukemic cell growth and development but also tuning their responsiveness to treatments. The list of mechanisms driven by MSCs to promote a leukemia drug-resistant phenotype has progressively expanded. Moreover, the relative proportion and the activation status of immune cells in the BM leukemic microenvironment may vary by influencing their reactivity against leukemic cells. In that, the capacity of the stroma to re-program immune cells, thus promoting and/or hampering therapeutic efficacy, is emerging as a crucial aspect in AML biology, adding an extra layer of complexity. Current treatments for AML have mainly focused on eradicating leukemia cells, with little consideration for the leukemia-damaged BM niche. Increasing evidence on the contribution of stromal and immune cells in response to therapy underscores the need to hold the mutual interplay, which takes place in the BM. A careful dissection of these interactions will help provide novel applications for drugs already under experimentation and open a wide array of opportunities for new drug discovery.
format	article
author	Marilena Ciciarello Giulia Corradi Dorian Forte Michele Cavo Antonio Curti
author_facet	Marilena Ciciarello Giulia Corradi Dorian Forte Michele Cavo Antonio Curti
author_sort	Marilena Ciciarello
title	Emerging Bone Marrow Microenvironment-Driven Mechanisms of Drug Resistance in Acute Myeloid Leukemia: Tangle or Chance?
title_short	Emerging Bone Marrow Microenvironment-Driven Mechanisms of Drug Resistance in Acute Myeloid Leukemia: Tangle or Chance?
title_full	Emerging Bone Marrow Microenvironment-Driven Mechanisms of Drug Resistance in Acute Myeloid Leukemia: Tangle or Chance?
title_fullStr	Emerging Bone Marrow Microenvironment-Driven Mechanisms of Drug Resistance in Acute Myeloid Leukemia: Tangle or Chance?
title_full_unstemmed	Emerging Bone Marrow Microenvironment-Driven Mechanisms of Drug Resistance in Acute Myeloid Leukemia: Tangle or Chance?
title_sort	emerging bone marrow microenvironment-driven mechanisms of drug resistance in acute myeloid leukemia: tangle or chance?
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f5a7acbfc1d847669fca4b91a91523bf
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Emerging Bone Marrow Microenvironment-Driven Mechanisms of Drug Resistance in Acute Myeloid Leukemia: Tangle or Chance?

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