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20 results on '"Kevin C. Gantz"'

1. Supplementary Table 5 from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

The 1,287 genes targeted by the shRNA of the leukemia library.

Published
2023

2. Supplementary Table 3 from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

Standard hematologic parameters in SIRT5-/- mice and SIRT5+/+ littermates.

Published
2023

3. Supplementary Table 8 from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

Plasmids.

Published
2023

4. Supplementary Table 1 from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

Patient sample information.

Published
2023

5. Supplementary Table 7 from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

Antibodies.

Published
2023

6. Data from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

We discovered that the survival and growth of many primary acute myeloid leukemia (AML) samples and cell lines, but not normal CD34+ cells, are dependent on SIRT5, a lysine deacylase implicated in regulating multiple metabolic pathways. Dependence on SIRT5 is genotype agnostic and extends to RAS- and p53-mutated AML. Results were comparable between SIRT5 knockdown and SIRT5 inhibition using NRD167, a potent and selective SIRT5 inhibitor. Apoptosis induced by SIRT5 disruption is preceded by reductions in oxidative phosphorylation and glutamine utilization, and an increase in mitochondrial superoxide that is attenuated by ectopic superoxide dismutase 2. These data indicate that SIRT5 controls and coordinates several key metabolic pathways in AML and implicate SIRT5 as a vulnerability in AML.Significance:Reducing SIRT5 activity is detrimental to the survival of AML cells regardless of genotype, yet well tolerated by healthy hematopoietic cells. In mouse models, disrupting SIRT5 inhibits AML progression. SIRT5 controls several metabolic pathways that are required for leukemia cell survival. These results identify SIRT5 as a therapeutic target in AML.See related commentary by Li and Melnick, p. 198.

Published
2023

7. Supplementary Figures from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

All supplemental figures and legends.

Published
2023

8. Supplementary Table 4 from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

Next generation sequencing for 52 myeloid malignancies-related genes.

Published
2023

9. Supplementary Table 6 from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

Oligonucleotide sequences.

Published
2023

10. Supplementary Table 2 from SIRT5 Is a Druggable Metabolic Vulnerability in Acute Myeloid Leukemia

Author

Michael W. Deininger, Thomas O'Hare, Christian A. Olsen, Nima Rajabi, Jamshid S. Khorashad, Siddharth M. Iyer, Hannah M. Redwine, Kevin C. Gantz, James E. Cox, Angelo D'Alessandro, Julie A. Reisz, Christina M. Egbert, Joshua L. Andersen, Shawn C. Owen, William L. Heaton, Phillip M. Clair, Ami B. Patel, Alexandria van Scoyk, Michael J. Xiao, Hein Than, Matthew S. Zabriskie, Courtney L. Jones, Nadeem A. Vellore, Anna V. Senina, Jonathan M. Ahmann, Clinton C. Mason, Orlando Antelope, Brayden J. Halverson, Anthony D. Pomicter, Anca Franzini, and Dongqing Yan

Abstract

Ranked list of 1,287 genes from shRNA library screen in primary AML cells. The 1,287 genes assessed with an shRNA library screen were sorted by the second highest percentile fold change present in 2 shRNA and across 2 samples, with the 34 genes showing a fold change in the top 2 percent in more than 2 samples listed first.

Published
2023

11. Supplementary Figure 4 from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Supplementary Figure 4

Published
2023

12. Supplementary Methods, Legends from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Supplementary Methods, Legends

Published
2023

13. Supplementary Table 1 from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Supplementary Table 1

Published
2023

14. Supplementary Figure 1 from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Supplementary Figure 1

Published
2023

15. Supplementary Figure 3 from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Supplementary Figure 3

Published
2023

16. Supplementary Figure 2 from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Supplementary Figure 2

Published
2023

17. Data from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Purpose:Myelofibrosis is a hematopoietic stem cell neoplasm characterized by bone marrow reticulin fibrosis, extramedullary hematopoiesis, and frequent transformation to acute myeloid leukemia. Constitutive activation of JAK/STAT signaling through mutations in JAK2, CALR, or MPL is central to myelofibrosis pathogenesis. JAK inhibitors such as ruxolitinib reduce symptoms and improve quality of life, but are not curative and do not prevent leukemic transformation, defining a need to identify better therapeutic targets in myelofibrosis.Experimental Design:A short hairpin RNA library screening was performed on JAK2V617F-mutant HEL cells. Nuclear–cytoplasmic transport (NCT) genes including RAN and RANBP2 were among top candidates. JAK2V617F-mutant cell lines, human primary myelofibrosis CD34+ cells, and a retroviral JAK2V617F-driven myeloproliferative neoplasms mouse model were used to determine the effects of inhibiting NCT with selective inhibitors of nuclear export compounds KPT-330 (selinexor) or KPT-8602 (eltanexor).Results:JAK2V617F-mutant HEL, SET-2, and HEL cells resistant to JAK inhibition are exquisitely sensitive to RAN knockdown or pharmacologic inhibition by KPT-330 or KPT-8602. Inhibition of NCT selectively decreased viable cells and colony formation by myelofibrosis compared with cord blood CD34+ cells and enhanced ruxolitinib-mediated growth inhibition and apoptosis, both in newly diagnosed and ruxolitinib-exposed myelofibrosis cells. Inhibition of NCT in myelofibrosis CD34+ cells led to nuclear accumulation of p53. KPT-330 in combination with ruxolitinib-normalized white blood cells, hematocrit, spleen size, and architecture, and selectively reduced JAK2V617F-mutant cells in vivo.Conclusions:Our data implicate NCT as a potential therapeutic target in myelofibrosis and provide a rationale for clinical evaluation in ruxolitinib-exposed patients with myelofibrosis.

Published
2023

18. Supplementary Figure 5 from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Supplementary Figure 5

Published
2023

19. Supplementary Table 2 from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Supplementary Table 2

Published
2023

20. Supplementary Table 3-8 from Nuclear–Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

Author

Michael W. Deininger, Thomas O'Hare, Josef T. Prchal, Kenneth M. Boucher, Rodney R. Miles, Mohamed E. Salama, Todd W. Kelley, Jamshid S. Khorashad, Sharon Shacham, Erkan Baloglu, Brayden J. Halverson, Sabina I. Swierczek, Hannah M. Redwine, Kevin C. Gantz, Phillip M. Clair, Anna M. Eiring, William L. Heaton, Ami B. Patel, Hein Than, Qiang Wang, Jonathan M. Ahmann, Anna V. Senina, Clinton C. Mason, Srinivas Tantravahi, Anthony D. Pomicter, and Dongqing Yan

Abstract

Supplementary Table 3-8

Published
2023

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