Nature Communications (May 2022)
Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia
- Natalia Baran,
- Alessia Lodi,
- Yogesh Dhungana,
- Shelley Herbrich,
- Meghan Collins,
- Shannon Sweeney,
- Renu Pandey,
- Anna Skwarska,
- Shraddha Patel,
- Mathieu Tremblay,
- Vinitha Mary Kuruvilla,
- Antonio Cavazos,
- Mecit Kaplan,
- Marc O. Warmoes,
- Diogo Troggian Veiga,
- Ken Furudate,
- Shanti Rojas-Sutterin,
- Andre Haman,
- Yves Gareau,
- Anne Marinier,
- Helen Ma,
- Karine Harutyunyan,
- May Daher,
- Luciana Melo Garcia,
- Gheath Al-Atrash,
- Sujan Piya,
- Vivian Ruvolo,
- Wentao Yang,
- Sriram Saravanan Shanmugavelandy,
- Ningping Feng,
- Jason Gay,
- Di Du,
- Jun J. Yang,
- Fieke W. Hoff,
- Marcin Kaminski,
- Katarzyna Tomczak,
- R. Eric Davis,
- Daniel Herranz,
- Adolfo Ferrando,
- Elias J. Jabbour,
- M. Emilia Di Francesco,
- David T. Teachey,
- Terzah M. Horton,
- Steven Kornblau,
- Katayoun Rezvani,
- Guy Sauvageau,
- Mihai Gagea,
- Michael Andreeff,
- Koichi Takahashi,
- Joseph R. Marszalek,
- Philip L. Lorenzi,
- Jiyang Yu,
- Stefano Tiziani,
- Trang Hoang,
- Marina Konopleva
Affiliations
- Natalia Baran
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Alessia Lodi
- Department of Nutritional Sciences, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin
- Yogesh Dhungana
- St. Jude Graduate School of Biomedical Sciences, St. Jude Children’s Research Hospital
- Shelley Herbrich
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Meghan Collins
- Department of Nutritional Sciences, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin
- Shannon Sweeney
- Department of Nutritional Sciences, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin
- Renu Pandey
- Department of Nutritional Sciences, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin
- Anna Skwarska
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Shraddha Patel
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Mathieu Tremblay
- Institute for Research in Immunology and Cancer, The University of Montreal
- Vinitha Mary Kuruvilla
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Antonio Cavazos
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Mecit Kaplan
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center
- Marc O. Warmoes
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center
- Diogo Troggian Veiga
- The Jackson Laboratory for Genomic Medicine
- Ken Furudate
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Shanti Rojas-Sutterin
- Institute for Research in Immunology and Cancer, The University of Montreal
- Andre Haman
- Institute for Research in Immunology and Cancer, The University of Montreal
- Yves Gareau
- Institute for Research in Immunology and Cancer, The University of Montreal
- Anne Marinier
- Institute for Research in Immunology and Cancer, The University of Montreal
- Helen Ma
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Karine Harutyunyan
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- May Daher
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center
- Luciana Melo Garcia
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center
- Gheath Al-Atrash
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center
- Sujan Piya
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Vivian Ruvolo
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Wentao Yang
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- Sriram Saravanan Shanmugavelandy
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Ningping Feng
- TRACTION Platform, Therapeutics Discovery Division, University of Texas M. D. Anderson Cancer Center
- Jason Gay
- TRACTION Platform, Therapeutics Discovery Division, University of Texas M. D. Anderson Cancer Center
- Di Du
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center
- Jun J. Yang
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- Fieke W. Hoff
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Marcin Kaminski
- Department of Immunology, St. Jude Children’s Research Hospital
- Katarzyna Tomczak
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center
- R. Eric Davis
- Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
- Daniel Herranz
- Rutgers Robert Wood Johnson Medical School, Cancer Institute of New Jersey
- Adolfo Ferrando
- Irving Cancer Research Center, Columbia University Irving Medical Center
- Elias J. Jabbour
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- M. Emilia Di Francesco
- Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center
- David T. Teachey
- Perelman School of Medicine, The University of Pennsylvania
- Terzah M. Horton
- Texas Children’s Cancer Center, Baylor College of Medicine
- Steven Kornblau
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Katayoun Rezvani
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center
- Guy Sauvageau
- Institute for Research in Immunology and Cancer, The University of Montreal
- Mihai Gagea
- Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center
- Michael Andreeff
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Koichi Takahashi
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- Joseph R. Marszalek
- TRACTION Platform, Therapeutics Discovery Division, University of Texas M. D. Anderson Cancer Center
- Philip L. Lorenzi
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center
- Jiyang Yu
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Stefano Tiziani
- Department of Nutritional Sciences, Dell Pediatric Research Institute, Dell Medical School, The University of Texas at Austin
- Trang Hoang
- Institute for Research in Immunology and Cancer, The University of Montreal
- Marina Konopleva
- Department of Leukemia, The University of Texas MD Anderson Cancer Center
- DOI
- https://doi.org/10.1038/s41467-022-30396-3
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 20
Abstract
Notch1 is frequently activated promoting T-cell acute lymphoblastic leukaemia (T-ALL). Here, the authors show that Notch1 induces oxidative phosphorylation dependency in T-ALL and synergism when inhibiting both mitochondrial complex I and glutaminolysis in preclinical murine and human xenograft models.
