PMID- 33409153
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210111
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 10
DP  - 2020
TI  - Mitochondrial Bioenergetics at the Onset of Drug Resistance in Hematological 
      Malignancies: An Overview.
PG  - 604143
LID - 10.3389/fonc.2020.604143 [doi]
LID - 604143
AB  - The combined derangements in mitochondria network, function and dynamics can 
      affect metabolism and ATP production, redox homeostasis and apoptosis triggering, 
      contributing to cancer development in many different complex ways. In 
      hematological malignancies, there is a strong relationship between cellular 
      metabolism, mitochondrial bioenergetics, interconnections with supportive 
      microenvironment and drug resistance. Lymphoma and chronic lymphocytic leukemia 
      cells, e.g., adapt to intrinsic oxidative stress by increasing mitochondrial 
      biogenesis. In other hematological disorders such as myeloma, on the contrary, 
      bioenergetics changes, associated to increased mitochondrial fitness, derive from 
      the adaptive response to drug-induced stress. In the bone marrow niche, a reverse 
      Warburg effect has been recently described, consisting in metabolic changes 
      occurring in stromal cells in the attempt to metabolically support adjacent 
      cancer cells. Moreover, a physiological dynamic, based on mitochondria transfer, 
      between tumor cells and their supporting stromal microenvironment has been 
      described to sustain oxidative stress associated to proteostasis maintenance in 
      multiple myeloma and leukemia. Increased mitochondrial biogenesis of tumor cells 
      associated to acquisition of new mitochondria transferred by mesenchymal stromal 
      cells results in augmented ATP production through increased oxidative 
      phosphorylation (OX-PHOS), higher drug resistance, and resurgence after 
      treatment. Accordingly, targeting mitochondrial biogenesis, electron transfer, 
      mitochondrial DNA replication, or mitochondrial fatty acid transport increases 
      therapy efficacy. In this review, we summarize selected examples of the 
      mitochondrial derangements in hematological malignancies, which provide metabolic 
      adaptation and apoptosis resistance, also supported by the crosstalk with tumor 
      microenvironment. This field promises a rational design to improve target-therapy 
      including the metabolic phenotype.
CI  - Copyright (c) 2020 Barbato, Scandura, Puglisi, Cambria, La Spina, Palumbo, 
      Lazzarino, Tibullo, Di Raimondo, Giallongo and Romano.
FAU - Barbato, Alessandro
AU  - Barbato A
AD  - Department of Clinical and Experimental Medicine, University of Catania, Catania, 
      Italy.
FAU - Scandura, Grazia
AU  - Scandura G
AD  - Department of General Surgery and Medical-Surgical Specialties, University of 
      Catania, Catania, Italy.
FAU - Puglisi, Fabrizio
AU  - Puglisi F
AD  - Department of Clinical and Experimental Medicine, University of Catania, Catania, 
      Italy.
FAU - Cambria, Daniela
AU  - Cambria D
AD  - Department of Clinical and Experimental Medicine, University of Catania, Catania, 
      Italy.
FAU - La Spina, Enrico
AU  - La Spina E
AD  - Department of General Surgery and Medical-Surgical Specialties, University of 
      Catania, Catania, Italy.
FAU - Palumbo, Giuseppe Alberto
AU  - Palumbo GA
AD  - Department of Medical, Surgical Sciences and Advanced Technologies G.F. 
      Ingrassia, University of Catania, Catania, Italy.
FAU - Lazzarino, Giacomo
AU  - Lazzarino G
AD  - Saint Camillus International University of Health and Medical Sciences, Rome, 
      Italy.
FAU - Tibullo, Daniele
AU  - Tibullo D
AD  - Department of Biotechnological and Biomedical Sciences, University of Catania, 
      Catania, Italy.
FAU - Di Raimondo, Francesco
AU  - Di Raimondo F
AD  - Department of General Surgery and Medical-Surgical Specialties, University of 
      Catania, Catania, Italy.
FAU - Giallongo, Cesarina
AU  - Giallongo C
AD  - Department of Medical, Surgical Sciences and Advanced Technologies G.F. 
      Ingrassia, University of Catania, Catania, Italy.
FAU - Romano, Alessandra
AU  - Romano A
AD  - Department of Surgery and Medical Specialties, University of Catania, Catania, 
      Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20201221
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC7779674
OTO - NOTNLM
OT  - OX-PHOS
OT  - acute myeloid leukemia
OT  - chronic lymphatic leukemia
OT  - lymphoma
OT  - mitochondria
OT  - multiple myeloma
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest. The handling editor declared a past co-authorship with one 
      of the authors FR.
EDAT- 2021/01/08 06:00
MHDA- 2021/01/08 06:01
PMCR- 2020/01/01
CRDT- 2021/01/07 06:08
PHST- 2020/09/08 00:00 [received]
PHST- 2020/11/13 00:00 [accepted]
PHST- 2021/01/07 06:08 [entrez]
PHST- 2021/01/08 06:00 [pubmed]
PHST- 2021/01/08 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2020.604143 [doi]
PST - epublish
SO  - Front Oncol. 2020 Dec 21;10:604143. doi: 10.3389/fonc.2020.604143. eCollection 
      2020.