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1. Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium

Author

Sheth, Anagha Inguva., primary, Althoff, Mark J., additional, Tolison, Hunter, additional, Engel, Krysta, additional, Amaya, Maria L., additional, Krug, Anna E., additional, Young, Tracy N., additional, Minhajuddin, Mohammad, additional, Pei, Shanshan, additional, Patel, Sweta B., additional, Winters, Amanda, additional, Miller, Regan, additional, Shelton, Ian T., additional, St-Germain, Jonathan, additional, Ling, Tianyi, additional, Jones, Courtney L., additional, Raught, Brian, additional, Gillen, Austin E., additional, Ransom, Monica, additional, Staggs, Sarah, additional, Smith, Clayton A., additional, Pollyea, Daniel A., additional, Stevens, Brett M., additional, and Jordan, Craig T., additional

Published
2024
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2. AMPK/FIS1-Mediated Mitophagy Is Required for Self-Renewal of Human AML Stem Cells

Author

Pei, Shanshan, Minhajuddin, Mohammad, Adane, Biniam, Khan, Nabilah, Stevens, Brett M, Mack, Stephen C, Lai, Sisi, Rich, Jeremy N, Inguva, Anagha, Shannon, Kevin M, Kim, Hyunmin, Tan, Aik-Choon, Myers, Jason R, Ashton, John M, Neff, Tobias, Pollyea, Daniel A, Smith, Clayton A, and Jordan, Craig T

Subjects
Biochemistry and Cell Biology, Biological Sciences, Cancer, Rare Diseases, Stem Cell Research - Nonembryonic - Human, Stem Cell Research, Hematology, Stem Cell Research - Nonembryonic - Non-Human, Aetiology, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, AMP-Activated Protein Kinases, Animals, Cell Self Renewal, Cells, Cultured, Female, Humans, Leukemia, Myeloid, Acute, Membrane Proteins, Mice, Mice, Inbred NOD, Mice, Transgenic, Mitochondrial Proteins, Mitophagy, Neoplastic Stem Cells, Protein Kinase Inhibitors, Signal Transduction, AMPK, FIS1, GSK3, acute myeloid leukemia, differentiation, leukemia stem cells, mitochondrial dynamics, mitophagy, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Leukemia stem cells (LSCs) are thought to drive the genesis of acute myeloid leukemia (AML) as well as relapse following chemotherapy. Because of their unique biology, developing effective methods to eradicate LSCs has been a significant challenge. In the present study, we demonstrate that intrinsic overexpression of the mitochondrial dynamics regulator FIS1 mediates mitophagy activity that is essential for primitive AML cells. Depletion of FIS1 attenuates mitophagy and leads to inactivation of GSK3, myeloid differentiation, cell cycle arrest, and a profound loss of LSC self-renewal potential. Further, we report that the central metabolic stress regulator AMPK is also intrinsically activated in LSC populations and is upstream of FIS1. Inhibition of AMPK signaling recapitulates the biological effect of FIS1 loss. These data suggest a model in which LSCs co-opt AMPK/FIS1-mediated mitophagy as a means to maintain stem cell properties that may be otherwise compromised by the stresses induced by oncogenic transformation.

Published
2018

5. Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia

Author

Winters, Amanda C., Gutman, Jonathan A., Purev, Enkhtsetseg, Nakic, Molly, Tobin, Jennifer, Chase, Stephanie, Kaiser, Jeff, Lyle, Lindsey, Boggs, Chelsey, Halsema, Keri, Schowinsky, Jeffrey T., Rosser, Julie, Ewalt, Mark D., Siegele, Bradford, Rana, Vishal, Schuster, Steven, Abbott, Diana, Stevens, Brett M., Jordan, Craig T., Smith, Clayton, and Pollyea, Daniel A.

Published
2019
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7. Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium

Author

Sheth, Anagha Inguva, primary, Engel, Krysta, additional, Tolison, Hunter, additional, Althoff, Mark J, additional, Amaya, Maria L., additional, Krug, Anna, additional, Young, Tracy, additional, Pei, Shanshan, additional, Patel, Sweta B., additional, Minhajuddin, Mohammad, additional, Winters, Amanda, additional, Miller, Regan, additional, Shelton, Ian, additional, St-Germain, Jonathan, additional, Ling, Tianyi, additional, Jones, Courtney, additional, Raught, Brian, additional, Gillen, Austin, additional, Ransom, Monica, additional, Staggs, Sarah, additional, Smith, Clayton A., additional, Pollyea, Daniel A., additional, Stevens, Brett M., additional, and Jordan, Craig T., additional

Published
2023
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8. Supplementary Table 6 from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., primary, Gillen, Austin E., primary, Stevens, Brett M., primary, Gasparetto, Maura, primary, Wang, Yanan, primary, Liu, Lina, primary, Liu, Jun, primary, Brunetti, Tonya M., primary, Engel, Krysta, primary, Staggs, Sarah, primary, Showers, William, primary, Sheth, Anagha Inguva, primary, Amaya, Maria L., primary, Minhajuddin, Mohammad, primary, Winters, Amanda, primary, Patel, Sweta B., primary, Tolison, Hunter, primary, Krug, Anna E., primary, Young, Tracy N., primary, Schowinsky, Jeffrey, primary, McMahon, Christine M., primary, Smith, Clayton A., primary, Pollyea, Daniel A., primary, and Jordan, Craig T., primary

Published
2023
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9. Supplementary Table 2 from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., primary, Gillen, Austin E., primary, Stevens, Brett M., primary, Gasparetto, Maura, primary, Wang, Yanan, primary, Liu, Lina, primary, Liu, Jun, primary, Brunetti, Tonya M., primary, Engel, Krysta, primary, Staggs, Sarah, primary, Showers, William, primary, Sheth, Anagha Inguva, primary, Amaya, Maria L., primary, Minhajuddin, Mohammad, primary, Winters, Amanda, primary, Patel, Sweta B., primary, Tolison, Hunter, primary, Krug, Anna E., primary, Young, Tracy N., primary, Schowinsky, Jeffrey, primary, McMahon, Christine M., primary, Smith, Clayton A., primary, Pollyea, Daniel A., primary, and Jordan, Craig T., primary

Published
2023
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10. Supplementary Table 8 from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., primary, Gillen, Austin E., primary, Stevens, Brett M., primary, Gasparetto, Maura, primary, Wang, Yanan, primary, Liu, Lina, primary, Liu, Jun, primary, Brunetti, Tonya M., primary, Engel, Krysta, primary, Staggs, Sarah, primary, Showers, William, primary, Sheth, Anagha Inguva, primary, Amaya, Maria L., primary, Minhajuddin, Mohammad, primary, Winters, Amanda, primary, Patel, Sweta B., primary, Tolison, Hunter, primary, Krug, Anna E., primary, Young, Tracy N., primary, Schowinsky, Jeffrey, primary, McMahon, Christine M., primary, Smith, Clayton A., primary, Pollyea, Daniel A., primary, and Jordan, Craig T., primary

Published
2023
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11. Supplementary Tables 3-5 from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., primary, Gillen, Austin E., primary, Stevens, Brett M., primary, Gasparetto, Maura, primary, Wang, Yanan, primary, Liu, Lina, primary, Liu, Jun, primary, Brunetti, Tonya M., primary, Engel, Krysta, primary, Staggs, Sarah, primary, Showers, William, primary, Sheth, Anagha Inguva, primary, Amaya, Maria L., primary, Minhajuddin, Mohammad, primary, Winters, Amanda, primary, Patel, Sweta B., primary, Tolison, Hunter, primary, Krug, Anna E., primary, Young, Tracy N., primary, Schowinsky, Jeffrey, primary, McMahon, Christine M., primary, Smith, Clayton A., primary, Pollyea, Daniel A., primary, and Jordan, Craig T., primary

Published
2023
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12. Supplementary Table 7 from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., primary, Gillen, Austin E., primary, Stevens, Brett M., primary, Gasparetto, Maura, primary, Wang, Yanan, primary, Liu, Lina, primary, Liu, Jun, primary, Brunetti, Tonya M., primary, Engel, Krysta, primary, Staggs, Sarah, primary, Showers, William, primary, Sheth, Anagha Inguva, primary, Amaya, Maria L., primary, Minhajuddin, Mohammad, primary, Winters, Amanda, primary, Patel, Sweta B., primary, Tolison, Hunter, primary, Krug, Anna E., primary, Young, Tracy N., primary, Schowinsky, Jeffrey, primary, McMahon, Christine M., primary, Smith, Clayton A., primary, Pollyea, Daniel A., primary, and Jordan, Craig T., primary

Published
2023
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13. Supplementary Table 1 from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., primary, Gillen, Austin E., primary, Stevens, Brett M., primary, Gasparetto, Maura, primary, Wang, Yanan, primary, Liu, Lina, primary, Liu, Jun, primary, Brunetti, Tonya M., primary, Engel, Krysta, primary, Staggs, Sarah, primary, Showers, William, primary, Sheth, Anagha Inguva, primary, Amaya, Maria L., primary, Minhajuddin, Mohammad, primary, Winters, Amanda, primary, Patel, Sweta B., primary, Tolison, Hunter, primary, Krug, Anna E., primary, Young, Tracy N., primary, Schowinsky, Jeffrey, primary, McMahon, Christine M., primary, Smith, Clayton A., primary, Pollyea, Daniel A., primary, and Jordan, Craig T., primary

Published
2023
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14. Supplementary Table 9 from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., primary, Gillen, Austin E., primary, Stevens, Brett M., primary, Gasparetto, Maura, primary, Wang, Yanan, primary, Liu, Lina, primary, Liu, Jun, primary, Brunetti, Tonya M., primary, Engel, Krysta, primary, Staggs, Sarah, primary, Showers, William, primary, Sheth, Anagha Inguva, primary, Amaya, Maria L., primary, Minhajuddin, Mohammad, primary, Winters, Amanda, primary, Patel, Sweta B., primary, Tolison, Hunter, primary, Krug, Anna E., primary, Young, Tracy N., primary, Schowinsky, Jeffrey, primary, McMahon, Christine M., primary, Smith, Clayton A., primary, Pollyea, Daniel A., primary, and Jordan, Craig T., primary

Published
2023
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15. Supplementary Figures S1-S7 from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., primary, Gillen, Austin E., primary, Stevens, Brett M., primary, Gasparetto, Maura, primary, Wang, Yanan, primary, Liu, Lina, primary, Liu, Jun, primary, Brunetti, Tonya M., primary, Engel, Krysta, primary, Staggs, Sarah, primary, Showers, William, primary, Sheth, Anagha Inguva, primary, Amaya, Maria L., primary, Minhajuddin, Mohammad, primary, Winters, Amanda, primary, Patel, Sweta B., primary, Tolison, Hunter, primary, Krug, Anna E., primary, Young, Tracy N., primary, Schowinsky, Jeffrey, primary, McMahon, Christine M., primary, Smith, Clayton A., primary, Pollyea, Daniel A., primary, and Jordan, Craig T., primary

Published
2023
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16. Data from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., primary, Gillen, Austin E., primary, Stevens, Brett M., primary, Gasparetto, Maura, primary, Wang, Yanan, primary, Liu, Lina, primary, Liu, Jun, primary, Brunetti, Tonya M., primary, Engel, Krysta, primary, Staggs, Sarah, primary, Showers, William, primary, Sheth, Anagha Inguva, primary, Amaya, Maria L., primary, Minhajuddin, Mohammad, primary, Winters, Amanda, primary, Patel, Sweta B., primary, Tolison, Hunter, primary, Krug, Anna E., primary, Young, Tracy N., primary, Schowinsky, Jeffrey, primary, McMahon, Christine M., primary, Smith, Clayton A., primary, Pollyea, Daniel A., primary, and Jordan, Craig T., primary

Published
2023
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17. Venetoclax with azacitidine disrupts energy metabolism and targets leukemia stem cells in patients with acute myeloid leukemia

Author

Pollyea, Daniel A., Stevens, Brett M., Jones, Courtney L., Winters, Amanda, Pei, Shanshan, Minhajuddin, Mohammad, D’Alessandro, Angelo, Culp-Hill, Rachel, Riemondy, Kent A., Gillen, Austin E., Hesselberth, Jay R., Abbott, Diana, Schatz, Derek, Gutman, Jonathan A., Purev, Enkhtsetseg, Smith, Clayton, and Jordan, Craig T.

Published
2018
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18. A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Author

Pei, Shanshan, primary, Shelton, Ian T., additional, Gillen, Austin E., additional, Stevens, Brett M., additional, Gasparetto, Maura, additional, Wang, Yanan, additional, Liu, Lina, additional, Liu, Jun, additional, Brunetti, Tonya M., additional, Engel, Krysta, additional, Staggs, Sarah, additional, Showers, William, additional, Sheth, Anagha Inguva, additional, Amaya, Maria L., additional, Minhajuddin, Mohammad, additional, Winters, Amanda, additional, Patel, Sweta B., additional, Tolison, Hunter, additional, Krug, Anna E., additional, Young, Tracy N., additional, Schowinsky, Jeffrey, additional, McMahon, Christine M., additional, Smith, Clayton A., additional, Pollyea, Daniel A., additional, and Jordan, Craig T., additional

Published
2023
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21. CD46–ADC Reduces the Engraftment of Multiple Myeloma Patient-Derived Xenografts.

Author

VanWyngarden, Michael J., Walker, Zachary J., Su, Yang, Perez de Acha, Olivia, Stevens, Brett M., Forsberg, Peter A., Mark, Tomer M., Matsui, William, Liu, Bin, and Sherbenou, Daniel W.

Subjects
THERAPEUTIC use of monoclonal antibodies, IN vitro studies, FLOW cytometry, DRUG efficacy, STATISTICS, XENOGRAFTS, IN vivo studies, ANALYSIS of variance, ALDEHYDE dehydrogenase, T-test (Statistics), ENZYME-linked immunosorbent assay, DESCRIPTIVE statistics, RESEARCH funding, MULTIPLE myeloma, TUMOR antigens, CELL lines, HEMATOPOIETIC stem cells, DATA analysis software, DATA analysis, ANTIGENS, PHENOTYPES, MICE
Abstract

Simple Summary: Multiple myeloma (MM) is incurable, implying that the disease cells are inherently resistant to current agents and inevitably lead to relapse. One strategy to improve the treatment paradigm is to pursue novel drug targets that are associated with relapsed disease. Towards this end, we developed a novel antibody–drug conjugate (ADC) that targets the cell surface complement inhibitor CD46. Here, we study the potential of this new agent to affect disease initiation. The gene encoding for CD46 is amplified on chromosome 1q in the majority of relapsed myeloma patients, as well as cells containing stem-like aldehyde dehydrogenase activity. We demonstrate the curative potential of CD46–ADC via its ability to abrogate disease engraftment of primary MM cell xenografts. In combination with a recent clinical trial, this study supports the continued study of CD46 as a therapeutic target in MM. An antibody–drug conjugate (ADC) targeting CD46 conjugated to monomethyl auristatin has a potent anti-myeloma effect in cell lines in vitro and in vivo, and patient samples treated ex vivo. Here, we tested if CD46–ADC may have the potential to target MM-initiating cells (MM-ICs). CD46 expression was measured on primary MM cells with a stem-like phenotype. A patient-derived xenograft (PDX) model was implemented utilizing implanted fetal bone fragments to provide a humanized microenvironment. Engraftment was monitored via serum human light chain ELISA, and at sacrifice via bone marrow and bone fragment flow cytometry. We then tested MM regeneration in PDX by treating mice with CD46–ADC or the nonbinding control–ADC. MM progenitor cells from patients that exhibit high aldehyde dehydrogenase activity also have a high expression of CD46. In PDX, newly diagnosed MM patient samples engrafted significantly more compared to relapsed/refractory samples. In mice transplanted with newly diagnosed samples, CD46–ADC treatment showed significantly decreased engraftment compared to control–ADC treatment. Our data further support the targeting of CD46 in MM. To our knowledge, this is the first study to show preclinical drug efficacy in a PDX model of MM. This is an important area for future study, as patient samples but not cell lines accurately represent intratumoral heterogeneity. [ABSTRACT FROM AUTHOR]

Published
2023
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22. Supplementary Figures S1-S5 from Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Patients with Acute Myeloid Leukemia

Author

Pei, Shanshan, primary, Pollyea, Daniel A., primary, Gustafson, Annika, primary, Stevens, Brett M., primary, Minhajuddin, Mohammad, primary, Fu, Rui, primary, Riemondy, Kent A., primary, Gillen, Austin E., primary, Sheridan, Ryan M., primary, Kim, Jihye, primary, Costello, James C., primary, Amaya, Maria L., primary, Inguva, Anagha, primary, Winters, Amanda, primary, Ye, Haobin, primary, Krug, Anna, primary, Jones, Courtney L., primary, Adane, Biniam, primary, Khan, Nabilah, primary, Ponder, Jessica, primary, Schowinsky, Jeffrey, primary, Abbott, Diana, primary, Hammes, Andrew, primary, Myers, Jason R., primary, Ashton, John M., primary, Nemkov, Travis, primary, D'Alessandro, Angelo, primary, Gutman, Jonathan A., primary, Ramsey, Haley E., primary, Savona, Michael R., primary, Smith, Clayton A., primary, and Jordan, Craig T., primary

Published
2023
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23. Data from The Hepatic Microenvironment Uniquely Protects Leukemia Cells through Induction of Growth and Survival Pathways Mediated by LIPG

Author

Ye, Haobin, primary, Minhajuddin, Mohammad, primary, Krug, Anna, primary, Pei, Shanshan, primary, Chou, Chih-Hsing, primary, Culp-Hill, Rachel, primary, Ponder, Jessica, primary, De Bloois, Erik, primary, Schniedewind, Björn, primary, Amaya, Maria L., primary, Inguva, Anagha, primary, Stevens, Brett M., primary, Pollyea, Daniel A., primary, Christians, Uwe, primary, Grimes, H. Leighton, primary, D'Alessandro, Angelo, primary, and Jordan, Craig T., primary

Published
2023
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24. Supplementary Tables S1-S6 from Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Patients with Acute Myeloid Leukemia

Author

Pei, Shanshan, primary, Pollyea, Daniel A., primary, Gustafson, Annika, primary, Stevens, Brett M., primary, Minhajuddin, Mohammad, primary, Fu, Rui, primary, Riemondy, Kent A., primary, Gillen, Austin E., primary, Sheridan, Ryan M., primary, Kim, Jihye, primary, Costello, James C., primary, Amaya, Maria L., primary, Inguva, Anagha, primary, Winters, Amanda, primary, Ye, Haobin, primary, Krug, Anna, primary, Jones, Courtney L., primary, Adane, Biniam, primary, Khan, Nabilah, primary, Ponder, Jessica, primary, Schowinsky, Jeffrey, primary, Abbott, Diana, primary, Hammes, Andrew, primary, Myers, Jason R., primary, Ashton, John M., primary, Nemkov, Travis, primary, D'Alessandro, Angelo, primary, Gutman, Jonathan A., primary, Ramsey, Haley E., primary, Savona, Michael R., primary, Smith, Clayton A., primary, and Jordan, Craig T., primary

Published
2023
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25. Supplementary Data from The Hepatic Microenvironment Uniquely Protects Leukemia Cells through Induction of Growth and Survival Pathways Mediated by LIPG

Author

Ye, Haobin, primary, Minhajuddin, Mohammad, primary, Krug, Anna, primary, Pei, Shanshan, primary, Chou, Chih-Hsing, primary, Culp-Hill, Rachel, primary, Ponder, Jessica, primary, De Bloois, Erik, primary, Schniedewind, Björn, primary, Amaya, Maria L., primary, Inguva, Anagha, primary, Stevens, Brett M., primary, Pollyea, Daniel A., primary, Christians, Uwe, primary, Grimes, H. Leighton, primary, D'Alessandro, Angelo, primary, and Jordan, Craig T., primary

Published
2023
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26. Data from Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Patients with Acute Myeloid Leukemia

Author

Pei, Shanshan, primary, Pollyea, Daniel A., primary, Gustafson, Annika, primary, Stevens, Brett M., primary, Minhajuddin, Mohammad, primary, Fu, Rui, primary, Riemondy, Kent A., primary, Gillen, Austin E., primary, Sheridan, Ryan M., primary, Kim, Jihye, primary, Costello, James C., primary, Amaya, Maria L., primary, Inguva, Anagha, primary, Winters, Amanda, primary, Ye, Haobin, primary, Krug, Anna, primary, Jones, Courtney L., primary, Adane, Biniam, primary, Khan, Nabilah, primary, Ponder, Jessica, primary, Schowinsky, Jeffrey, primary, Abbott, Diana, primary, Hammes, Andrew, primary, Myers, Jason R., primary, Ashton, John M., primary, Nemkov, Travis, primary, D'Alessandro, Angelo, primary, Gutman, Jonathan A., primary, Ramsey, Haley E., primary, Savona, Michael R., primary, Smith, Clayton A., primary, and Jordan, Craig T., primary

Published
2023
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27. Supplemental Methods from Tyrosine Kinase Inhibition in Leukemia Induces an Altered Metabolic State Sensitive to Mitochondrial Perturbations

Author

Alvarez-Calderon, Francesca, primary, Gregory, Mark A., primary, Pham-Danis, Catherine, primary, DeRyckere, Deborah, primary, Stevens, Brett M., primary, Zaberezhnyy, Vadym, primary, Hill, Amanda A., primary, Gemta, Lelisa, primary, Kumar, Amit, primary, Kumar, Vijay, primary, Wempe, Michael F., primary, Pollyea, Daniel A., primary, Jordan, Craig T., primary, Serkova, Natalie J., primary, Graham, Douglas K., primary, and DeGregori, James, primary

Published
2023
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28. Supplemental Figures 1-8 from Tyrosine Kinase Inhibition in Leukemia Induces an Altered Metabolic State Sensitive to Mitochondrial Perturbations

Author

Alvarez-Calderon, Francesca, primary, Gregory, Mark A., primary, Pham-Danis, Catherine, primary, DeRyckere, Deborah, primary, Stevens, Brett M., primary, Zaberezhnyy, Vadym, primary, Hill, Amanda A., primary, Gemta, Lelisa, primary, Kumar, Amit, primary, Kumar, Vijay, primary, Wempe, Michael F., primary, Pollyea, Daniel A., primary, Jordan, Craig T., primary, Serkova, Natalie J., primary, Graham, Douglas K., primary, and DeGregori, James, primary

Published
2023
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29. Supplemental Tables 1-4 from Tyrosine Kinase Inhibition in Leukemia Induces an Altered Metabolic State Sensitive to Mitochondrial Perturbations

Author

Alvarez-Calderon, Francesca, primary, Gregory, Mark A., primary, Pham-Danis, Catherine, primary, DeRyckere, Deborah, primary, Stevens, Brett M., primary, Zaberezhnyy, Vadym, primary, Hill, Amanda A., primary, Gemta, Lelisa, primary, Kumar, Amit, primary, Kumar, Vijay, primary, Wempe, Michael F., primary, Pollyea, Daniel A., primary, Jordan, Craig T., primary, Serkova, Natalie J., primary, Graham, Douglas K., primary, and DeGregori, James, primary

Published
2023
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30. Supplementary Data from Exploiting Protein Translation Dependence in Multiple Myeloma with Omacetaxine-Based Therapy

Author

Walker, Zachary J., primary, Idler, Beau M., primary, Davis, Lorraine N., primary, Stevens, Brett M., primary, VanWyngarden, Michael J., primary, Ohlstrom, Denis, primary, Bearrows, Shelby C., primary, Hammes, Andrew, primary, Smith, Clayton A., primary, Jordan, Craig T., primary, Mark, Tomer M., primary, Forsberg, Peter A., primary, and Sherbenou, Daniel W., primary

Published
2023
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32. A novel type of monocytic leukemia stem cell revealed by the clinical use of venetoclax-based therapy

Author

Pei, Shanshan, primary, Gillen, Austin E, additional, Shelton, Ian T, additional, Stevens, Brett M, additional, Gasparetto, Maura, additional, Engel, Krysta, additional, Staggs, Sarah, additional, Wang, Yanan, additional, Showers, William, additional, Inguva, Anagha, additional, Amaya, Maria L, additional, Minhajuddin, Mohammad, additional, Winters, Amanda, additional, Patel, Sweta B, additional, Tolison, Hunter, additional, Krug, Anna, additional, Young, Tracy N, additional, Schowinsky, Jeffrey, additional, McMahon, Christine, additional, Smith, Clayton A, additional, Pollyea, Daniel A, additional, and Jordan, Craig T, additional

Published
2022
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34. Higher-Dose Venetoclax with Measurable Residual Disease-Guided Azacitidine Discontinuation in Newly Diagnosed Patients with Acute Myeloid Leukemia: Phase 2 Hiddav Study

Author

Gutman, Jonathan A., primary, Winters, Amanda C., additional, Kent, Andrew, additional, Amaya, Maria L., additional, McMahon, Christine M., additional, Smith, Clayton, additional, Jordan, Craig T, additional, Stevens, Brett M., additional, Minhajuddin, Mohammad, additional, Pei, Shanshan, additional, Schowinsky, Jeffrey, additional, Tobin, Jennifer, additional, O'Brien, Kelly, additional, Falco, Angela, additional, Taylor, Elizabeth, additional, Brecl, Constance, additional, Ho, Phuong, additional, Sohalski, Connor, additional, Dell-Martin, Jessica, additional, Ondracek, Olivia, additional, Abbott, Diana, additional, and Pollyea, Daniel A., additional

Published
2022
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35. Intracellular Calcium Localization Mediates the Activity of Venetoclax in Targeting Acute Myeloid Leukemia Stem Cells

Author

Inguva, Anagha, primary, Engel, Krysta L., additional, Tolison, Hunter, additional, Althoff, Mark J, additional, Pei, Shanshan, additional, Amaya, Maria L., additional, Krug, Anna, additional, Minhajuddin, Mohammad, additional, Jones, Courtney L, additional, Gillen, Austin E., additional, Ransom, Monica, additional, Staggs, Sarah, additional, Pollyea, Daniel A., additional, Smith, Clayton, additional, Stevens, Brett M., additional, and Jordan, Craig T., additional

Published
2022
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36. Response to Intensive Induction Chemotherapy after Failure of Frontline Azacitidine+Venetoclax in Acute Myeloid Leukemia

Author

McMahon, Christine M., primary, Gil, Kellen, additional, Amaya, Maria L., additional, Gutman, Jonathan A., additional, Hayden, Alexander, additional, Schwartz, Marc, additional, Bosma, Grace, additional, Abbott, Diana, additional, Stevens, Brett M., additional, Smith, Clayton, additional, Jordan, Craig T, additional, and Pollyea, Daniel A., additional

Published
2022
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41. Therapy-Resistant Acute Myeloid Leukemia Stem Cells Are Resensitized to Venetoclax + Azacitidine by Targeting Fatty Acid Desaturases 1 and 2.

Author

Culp-Hill, Rachel, Stevens, Brett M., Jones, Courtney L., Pei, Shanshan, Dzieciatkowska, Monika, Minhajuddin, Mohammad, Jordan, Craig T., and D'Alessandro, Angelo

Subjects
FATTY acid desaturase, ACUTE myeloid leukemia, VENETOCLAX, STEM cells, AZACITIDINE, NAD (Coenzyme)
Abstract

Recent advances in targeting leukemic stem cells (LSCs) using venetoclax with azacitidine (ven + aza) has significantly improved outcomes for de novo acute myeloid leukemia (AML) patients. However, patients who relapse after traditional chemotherapy are often venetoclax-resistant and exhibit poor clinical outcomes. We previously described that fatty acid metabolism drives oxidative phosphorylation (OXPHOS) and acts as a mechanism of LSC survival in relapsed/refractory AML. Here, we report that chemotherapy-relapsed primary AML displays aberrant fatty acid and lipid metabolism, as well as increased fatty acid desaturation through the activity of fatty acid desaturases 1 and 2, and that fatty acid desaturases function as a mechanism of recycling NAD+ to drive relapsed LSC survival. When combined with ven + aza, the genetic and pharmacologic inhibition of fatty acid desaturation results in decreased primary AML viability in relapsed AML. This study includes the largest lipidomic profile of LSC-enriched primary AML patient cells to date and indicates that inhibition of fatty acid desaturation is a promising therapeutic target for relapsed AML. [ABSTRACT FROM AUTHOR]

Published
2023
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43. Lysosomal Acid Lipase a (LIPA) Modulates Leukemia Stem Cell (LSC) Response to Venetoclax/TKI Combination Therapy in Blast Phase Chronic Myeloid Leukemia

Author

Minhajuddin, Mohd, primary, Ye, Haobin, additional, Winters, Amanda C., additional, Pei, Shanshan, additional, Khan, Nabilah, additional, Stevens, Brett M., additional, Adane, Biniam, additional, Amaya, Maria L., additional, Inguva, Anagha, additional, Krug, Anna, additional, Gasparetto, Maura, additional, Sherbenou, Daniel W., additional, Pollyea, Daniel A., additional, Smith, Clayton, additional, and Jordan, Craig T., additional

Published
2021
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46. Targeting MDS Stem Cells with Omacetaxine and Azacitidine for Newly Diagnosed High Grade Patients: Phase 1 Trial Results and Preliminary Mechanistic Studies

Author

Stevens, Brett M., primary, Winters, Amanda C., additional, Minhajuddin, Mohammad, additional, Amaya, Maria L., additional, McMahon, Christine M., additional, Gutman, Jonathan A., additional, Smith, Clayton, additional, Wang, Deng, additional, Adkins, Connor, additional, Ondracek, Olivia, additional, Jordan, Craig T., additional, and Pollyea, Daniel A., additional

Published
2021
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50. PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress

Author

Chavez, James S., primary, Rabe, Jennifer L., additional, Loeffler, Dirk, additional, Higa, Kelly C., additional, Hernandez, Giovanny, additional, Mills, Taylor S., additional, Ahmed, Nouraiz, additional, Gessner, Rachel L., additional, Ke, Zhonghe, additional, Idler, Beau M., additional, Niño, Katia E., additional, Kim, Hyunmin, additional, Myers, Jason R., additional, Stevens, Brett M., additional, Davizon-Castillo, Pavel, additional, Jordan, Craig T., additional, Nakajima, Hideaki, additional, Ashton, John, additional, Welner, Robert S., additional, Schroeder, Timm, additional, DeGregori, James, additional, and Pietras, Eric M., additional

Published
2021
Full Text
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