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Inhibition of mitochondrial translation overcomes venetoclax resistance in AML through activation of the integrated stress response.

Sharon D, Cathelin S, Mirali S, Di Trani JM, Yanofsky DJ, Keon KA, Rubinstein JL, Schimmer AD, Ketela T, Chan SM.

Sci Transl Med. 2019 Oct 30;11(516). pii: eaax2863. doi: 10.1126/scitranslmed.aax2863.


Tafazzin modulates cellular phospholipid composition to regulate AML stemness.

Seneviratne AK, Xu M, Schimmer AD.

Mol Cell Oncol. 2019 Jun 11;6(5):e1620051. doi: 10.1080/23723556.2019.1620051. eCollection 2019.


Impact of preleukemic mutations and their persistence on hematologic recovery after induction chemotherapy for AML.

Murphy T, Zou J, Daher-Reyes GS, Arruda A, Gupta V, McNamara CJ, Minden MD, Schimmer AD, Sibai H, Yee KWL, Korulla M, Stockley T, Kamel-Reid S, Maze D, Tierens A, Bratman SV, Schuh AC, Chan SM.

Blood Adv. 2019 Aug 13;3(15):2307-2311. doi: 10.1182/bloodadvances.2019000306. No abstract available.


Phospholipid metabolism regulates AML growth and stemness.

Xu M, Seneviratne AK, Schimmer AD.

Aging (Albany NY). 2019 Jun 25;11(12):3895-3897. doi: 10.18632/aging.102055. No abstract available.


De Novo Design of Boron-Based Peptidomimetics as Potent Inhibitors of Human ClpP in the Presence of Human ClpX.

Tan J, Grouleff JJ, Jitkova Y, Diaz DB, Griffith EC, Shao W, Bogdanchikova AF, Poda G, Schimmer AD, Lee RE, Yudin AK.

J Med Chem. 2019 Jul 11;62(13):6377-6390. doi: 10.1021/acs.jmedchem.9b00878. Epub 2019 Jun 26.


The Mitochondrial Transacylase, Tafazzin, Regulates AML Stemness by Modulating Intracellular Levels of Phospholipids.

Seneviratne AK, Xu M, Aristizabal Henao JJ, Fajardo VA, Hao Z, Voisin V, Xu GW, Hurren R, Kim S, MacLean N, Wang X, Gronda M, Jeyaraju D, Jitkova Y, Ketela T, Mullokandov M, Sharon D, Thomas G, Chouinard-Watkins R, Hawley JR, Schafer C, Yau HL, Khuchua Z, Aman A, Al-Awar R, Gross A, Claypool SM, Bazinet RP, Lupien M, Chan S, De Carvalho DD, Minden MD, Bader GD, Stark KD, LeBlanc P, Schimmer AD.

Cell Stem Cell. 2019 Jun 6;24(6):1007. doi: 10.1016/j.stem.2019.04.020. No abstract available.


17-Hydroxy Wortmannin Restores TRAIL's Response by Ameliorating Increased Beclin 1 Level and Autophagy Function in TRAIL-Resistant Colon Cancer Cells.

Dai S, Yang S, Hu X, Sun W, Tawa G, Zhu W, Schimmer AD, He C, Fang B, Zhu H, Zheng W.

Mol Cancer Ther. 2019 Jul;18(7):1265-1277. doi: 10.1158/1535-7163.MCT-18-1241. Epub 2019 May 15.


Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality.

Ishizawa J, Zarabi SF, Davis RE, Halgas O, Nii T, Jitkova Y, Zhao R, St-Germain J, Heese LE, Egan G, Ruvolo VR, Barghout SH, Nishida Y, Hurren R, Ma W, Gronda M, Link T, Wong K, Mabanglo M, Kojima K, Borthakur G, MacLean N, Ma MCJ, Leber AB, Minden MD, Houry W, Kantarjian H, Stogniew M, Raught B, Pai EF, Schimmer AD, Andreeff M.

Cancer Cell. 2019 May 13;35(5):721-737.e9. doi: 10.1016/j.ccell.2019.03.014. Epub 2019 May 2.


The Mitochondrial Transacylase, Tafazzin, Regulates for AML Stemness by Modulating Intracellular Levels of Phospholipids.

Seneviratne AK, Xu M, Henao JJA, Fajardo VA, Hao Z, Voisin V, Xu GW, Hurren R, Kim S, MacLean N, Wang X, Gronda M, Jeyaraju D, Jitkova Y, Ketela T, Mullokandov M, Sharon D, Thomas G, Chouinard-Watkins R, Hawley JR, Schafer C, Yau HL, Khuchua Z, Aman A, Al-Awar R, Gross A, Claypool SM, Bazinet RP, Lupien M, Chan S, De Carvalho DD, Minden MD, Bader GD, Stark KD, LeBlanc P, Schimmer AD.

Cell Stem Cell. 2019 Apr 4;24(4):621-636.e16. doi: 10.1016/j.stem.2019.02.020. Epub 2019 Mar 28. Erratum in: Cell Stem Cell. 2019 Jun 6;24(6):1007.


The thymidine dideoxynucleoside analog, alovudine, inhibits the mitochondrial DNA polymerase γ, impairs oxidative phosphorylation and promotes monocytic differentiation in acute myeloid leukemia.

Yehudai D, Liyanage SU, Hurren R, Rizoska B, Albertella M, Gronda M, Jeyaraju DV, Wang X, Barghout SH, MacLean N, Siriwardena TP, Jitkova Y, Targett-Adams P, Schimmer AD.

Haematologica. 2019 May;104(5):963-972. doi: 10.3324/haematol.2018.195172. Epub 2018 Dec 20.


Pain in patients with newly diagnosed or relapsed acute leukemia.

Shaulov A, Rodin G, Popovic G, Caraiscos VB, Le LW, Rydall A, Schimmer AD, Zimmermann C.

Support Care Cancer. 2019 Aug;27(8):2789-2797. doi: 10.1007/s00520-018-4583-5. Epub 2018 Dec 8.


MTCH2-mediated mitochondrial fusion drives exit from naïve pluripotency in embryonic stem cells.

Bahat A, Goldman A, Zaltsman Y, Khan DH, Halperin C, Amzallag E, Krupalnik V, Mullokandov M, Silberman A, Erez A, Schimmer AD, Hanna JH, Gross A.

Nat Commun. 2018 Dec 3;9(1):5132. doi: 10.1038/s41467-018-07519-w.


Metabolic Flexibility in Leukemia-Adapt or Die.

Nachmias B, Schimmer AD.

Cancer Cell. 2018 Nov 12;34(5):695-696. doi: 10.1016/j.ccell.2018.10.012.


The ubiquitin-activating enzyme, UBA1, as a novel therapeutic target for AML.

Barghout SH, Schimmer AD.

Oncotarget. 2018 Sep 28;9(76):34198-34199. doi: 10.18632/oncotarget.26153. eCollection 2018 Sep 28. No abstract available.


A phase II open-label study of aprepitant as anti-emetic prophylaxis in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy.

Brandwein JM, Seki JT, Atenafu EG, Rostom A, Lutynski A, Rydlewski A, Schimmer AD, Schuh AC, Gupta V, Yee KWL.

Support Care Cancer. 2019 Jun;27(6):2295-2300. doi: 10.1007/s00520-018-4515-4. Epub 2018 Oct 19.


Acyldepsipeptide Analogs Dysregulate Human Mitochondrial ClpP Protease Activity and Cause Apoptotic Cell Death.

Wong KS, Mabanglo MF, Seraphim TV, Mollica A, Mao YQ, Rizzolo K, Leung E, Moutaoufik MT, Hoell L, Phanse S, Goodreid J, Barbosa LRS, Ramos CHI, Babu M, Mennella V, Batey RA, Schimmer AD, Houry WA.

Cell Chem Biol. 2018 Aug 16;25(8):1017-1030.e9. doi: 10.1016/j.chembiol.2018.05.014. Epub 2018 Jun 28.


Mitochondrial Shapeshifting Impacts AML Stemness and Differentiation.

Schimmer AD.

Cell Stem Cell. 2018 Jul 5;23(1):3-4. doi: 10.1016/j.stem.2018.05.026.


Preclinical evaluation of the selective small-molecule UBA1 inhibitor, TAK-243, in acute myeloid leukemia.

Barghout SH, Patel PS, Wang X, Xu GW, Kavanagh S, Halgas O, Zarabi SF, Gronda M, Hurren R, Jeyaraju DV, MacLean N, Brennan S, Hyer ML, Berger A, Traore T, Milhollen M, Smith AC, Minden MD, Pai EF, Hakem R, Schimmer AD.

Leukemia. 2019 Jan;33(1):37-51. doi: 10.1038/s41375-018-0167-0. Epub 2018 Jun 8.


Prevalence of oral lesions in and dental needs of patients with newly diagnosed acute leukemia.

Watson E, Wood RE, Maxymiw WG, Schimmer AD.

J Am Dent Assoc. 2018 Jun;149(6):470-480. doi: 10.1016/j.adaj.2018.01.019. Epub 2018 Mar 30.


AML refractory to primary induction with Ida-FLAG has a poor clinical outcome.

Kavanagh S, Heath E, Hurren R, Gronda M, Barghout SH, Liyanage SU, Siriwardena TP, Claudio J, Zhang T, Sukhai M, Stockley TL, Kamel-Reid S, Rostom A, Lutynski A, Khalaf D, Rydlewski A, Chan SM, Gupta V, Maze D, Sibai H, Schuh AC, Yee K, Minden MD, Schimmer AD.

Leuk Res. 2018 May;68:22-28. doi: 10.1016/j.leukres.2018.02.012. Epub 2018 Feb 20.


The importance of meaningful activity in people living with acute myeloid leukemia.

Deckert AL, Gheihman G, Nissim R, Chung C, Schimmer AD, Zimmermann C, Rodin G.

Leuk Res. 2018 Apr;67:86-91. doi: 10.1016/j.leukres.2018.02.009. Epub 2018 Feb 15.


Effect of an antimicrobial stewardship programme on antimicrobial utilisation and costs in patients with leukaemia: a retrospective controlled study.

So M, Mamdani MM, Morris AM, Lau TTY, Broady R, Deotare U, Grant J, Kim D, Schimmer AD, Schuh AC, Shajari S, Steinberg M, Bell CM, Husain S.

Clin Microbiol Infect. 2018 Aug;24(8):882-888. doi: 10.1016/j.cmi.2017.11.009. Epub 2017 Nov 11.


Emerging therapies for acute myeloid leukemia: translating biology into the clinic.

Kavanagh S, Murphy T, Law A, Yehudai D, Ho JM, Chan S, Schimmer AD.

JCI Insight. 2017 Sep 21;2(18). pii: 95679. doi: 10.1172/jci.insight.95679. eCollection 2017 Sep 21. Review.


Distribution and Impact of Comorbidities on Survival and Leukemic Transformation in Myeloproliferative Neoplasm-Associated Myelofibrosis: A Retrospective Cohort Study.

Bartoszko J, Panzarella T, McNamara CJ, Lau A, Schimmer AD, Schuh AC, Sibai H, Maze D, Yee KWL, Devlin R, Gupta V.

Clin Lymphoma Myeloma Leuk. 2017 Nov;17(11):774-781. doi: 10.1016/j.clml.2017.06.031. Epub 2017 Jun 29.


Novel Mitochondrial Mechanisms of Cytarabine Resistance in Primary AML Cells.

Schimmer AD.

Cancer Discov. 2017 Jul;7(7):670-672. doi: 10.1158/2159-8290.CD-17-0476.


Sharing post-AML consolidation supportive therapy with local centers reduces patient travel burden without compromising outcomes.

Hershenfeld SA, Maki K, Rothfels L, Murray CS, Nixon S, Schimmer AD, Doherty MC.

Leuk Res. 2017 Aug;59:93-96. doi: 10.1016/j.leukres.2017.05.023. Epub 2017 Jun 1.


Remissions after third induction chemotherapy for primary non-responders with acute myeloid leukemia (AML) are uncommon and short-lived.

Farshchi Zarabi S, Chan S, Gupta V, Khalaf D, Lutynski A, Minden MD, Rostom A, Rydlewski A, Schuh AC, Sibai H, Yee KWL, Schimmer AD.

Leuk Lymphoma. 2018 Jan;59(1):237-240. doi: 10.1080/10428194.2017.1323273. Epub 2017 Jun 9. No abstract available.


Expression of CD4 is correlated with an unfavorable prognosis in wild-type NPM1, FLT3-ITD-negative cytogenetically normal adult acute myeloid leukemia.

Guo RJ, Atenafu EG, Schimmer AD, Minden MD, Chang H.

Int J Lab Hematol. 2017 Aug;39(4):429-437. doi: 10.1111/ijlh.12649. Epub 2017 Mar 20.


Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML.

Liyanage SU, Hurren R, Voisin V, Bridon G, Wang X, Xu C, MacLean N, Siriwardena TP, Gronda M, Yehudai D, Sriskanthadevan S, Avizonis D, Shamas-Din A, Minden MD, Bader GD, Laposa R, Schimmer AD.

Blood. 2017 May 11;129(19):2657-2666. doi: 10.1182/blood-2016-10-741207. Epub 2017 Mar 10.


Biological and clinical consequences of NPM1 mutations in AML.

Heath EM, Chan SM, Minden MD, Murphy T, Shlush LI, Schimmer AD.

Leukemia. 2017 Apr;31(4):798-807. doi: 10.1038/leu.2017.30. Epub 2017 Jan 23. Review.


A 17-gene stemness score for rapid determination of risk in acute leukaemia.

Ng SW, Mitchell A, Kennedy JA, Chen WC, McLeod J, Ibrahimova N, Arruda A, Popescu A, Gupta V, Schimmer AD, Schuh AC, Yee KW, Bullinger L, Herold T, Görlich D, Büchner T, Hiddemann W, Berdel WE, Wörmann B, Cheok M, Preudhomme C, Dombret H, Metzeler K, Buske C, Löwenberg B, Valk PJ, Zandstra PW, Minden MD, Dick JE, Wang JC.

Nature. 2016 Dec 15;540(7633):433-437. doi: 10.1038/nature20598. Epub 2016 Dec 7.


Inhibiting glutaminase in acute myeloid leukemia: metabolic dependency of selected AML subtypes.

Matre P, Velez J, Jacamo R, Qi Y, Su X, Cai T, Chan SM, Lodi A, Sweeney SR, Ma H, Davis RE, Baran N, Haferlach T, Su X, Flores ER, Gonzalez D, Konoplev S, Samudio I, DiNardo C, Majeti R, Schimmer AD, Li W, Wang T, Tiziani S, Konopleva M.

Oncotarget. 2016 Nov 29;7(48):79722-79735. doi: 10.18632/oncotarget.12944.


Erlotinib synergizes with the poly(ADP-ribose) glycohydrolase inhibitor ethacridine in acute myeloid leukemia cells.

Rotin LE, MacLean N, Aman A, Gronda M, Lin FH, Hurren R, Wang X, Wrana JL, Datti A, Al-Awar R, Minden MD, Schimmer AD.

Haematologica. 2016 Nov;101(11):e449-e453. Epub 2016 Sep 1. No abstract available.


A Phase 1 study of intravenous infusions of tigecycline in patients with acute myeloid leukemia.

Reed GA, Schiller GJ, Kambhampati S, Tallman MS, Douer D, Minden MD, Yee KW, Gupta V, Brandwein J, Jitkova Y, Gronda M, Hurren R, Shamas-Din A, Schuh AC, Schimmer AD.

Cancer Med. 2016 Nov;5(11):3031-3040. doi: 10.1002/cam4.845. Epub 2016 Oct 13.


Venous thromboembolism prevention during asparaginase-based therapy for acute lymphoblastic leukemia.

Sibai H, Seki JT, Wang TQ, Sakurai N, Atenafu EG, Yee KW, Schuh AC, Gupta V, Minden MD, Schimmer AD, Brandwein JM.

Curr Oncol. 2016 Aug;23(4):e355-61. doi: 10.3747/co.23.3077. Epub 2016 Aug 12.


A phase I trial of the aurora kinase inhibitor, ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia.

Yee KW, Chen HW, Hedley DW, Chow S, Brandwein J, Schuh AC, Schimmer AD, Gupta V, Sanfelice D, Johnson T, Le LW, Arnott J, Bray MR, Sidor C, Minden MD.

Invest New Drugs. 2016 Oct;34(5):614-24. doi: 10.1007/s10637-016-0375-2. Epub 2016 Jul 12.


A novel isoflavone, ME-344, targets the cytoskeleton in acute myeloid leukemia.

Jeyaraju DV, Hurren R, Wang X, MacLean N, Gronda M, Shamas-Din A, Minden MD, Giaever G, Schimmer AD.

Oncotarget. 2016 Aug 2;7(31):49777-49785. doi: 10.18632/oncotarget.10446.


The ubiquitin ligase HERC4 mediates c-Maf ubiquitination and delays the growth of multiple myeloma xenografts in nude mice.

Zhang Z, Tong J, Tang X, Juan J, Cao B, Hurren R, Chen G, Taylor P, Xu X, Shi CX, Du J, Hou J, Wang G, Wu D, Stewart AK, Schimmer AD, Moran MF, Mao X.

Blood. 2016 Mar 31;127(13):1676-86. doi: 10.1182/blood-2015-07-658203. Epub 2016 Jan 29.


Auger electron-emitting (111)In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123(+)/CD131(-) phenotype of leukemia stem cells.

Gao C, Leyton JV, Schimmer AD, Minden M, Reilly RM.

Appl Radiat Isot. 2016 Apr;110:1-7. doi: 10.1016/j.apradiso.2015.12.043. Epub 2015 Dec 18.


A phase I study of elesclomol sodium in patients with acute myeloid leukemia.

Hedley D, Shamas-Din A, Chow S, Sanfelice D, Schuh AC, Brandwein JM, Seftel MD, Gupta V, Yee KW, Schimmer AD.

Leuk Lymphoma. 2016 Oct;57(10):2437-40. doi: 10.3109/10428194.2016.1138293. Epub 2016 Feb 5. No abstract available.


Investigating the synergistic mechanism between ibrutinib and daunorubicin in acute myeloid leukemia cells.

Rotin LE, Gronda M, Hurren R, Wang X, Minden MD, Slassi M, Schimmer AD.

Leuk Lymphoma. 2016 Oct;57(10):2432-6. doi: 10.3109/10428194.2016.1138292. Epub 2016 Feb 17. No abstract available.


Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.

Rotin LE, Gronda M, MacLean N, Hurren R, Wang X, Lin FH, Wrana J, Datti A, Barber DL, Minden MD, Slassi M, Schimmer AD.

Oncotarget. 2016 Jan 19;7(3):2765-79. doi: 10.18632/oncotarget.6409.


Targeting mitochondrial RNA polymerase in acute myeloid leukemia.

Bralha FN, Liyanage SU, Hurren R, Wang X, Son MH, Fung TA, Chingcuanco FB, Tung AY, Andreazza AC, Psarianos P, Schimmer AD, Salmena L, Laposa RR.

Oncotarget. 2015 Nov 10;6(35):37216-28. doi: 10.18632/oncotarget.6129.


Increased pressure alters plasma membrane dynamics and renders acute myeloid leukemia cells resistant to daunorubicin.

Nirmalanandhan VS, Hurren R, Cameron WD, Gronda M, Shamas-Din A, You L, Minden MD, Rocheleau JV, Schimmer AD.

Haematologica. 2015 Oct;100(10):e406-8. doi: 10.3324/haematol.2015.129866. Epub 2015 Jul 16. No abstract available.


FV-162 is a novel, orally bioavailable, irreversible proteasome inhibitor with improved pharmacokinetics displaying preclinical efficacy with continuous daily dosing.

Wang Z, Dove P, Wang X, Shamas-Din A, Li Z, Nachman A, Oh YJ, Hurren R, Ruschak A, Climie S, Press B, Griffin C, Undzys E, Aman A, Al-awar R, Kay LE, O'Neill D, Trudel S, Slassi M, Schimmer AD.

Cell Death Dis. 2015 Jul 9;6:e1815. doi: 10.1038/cddis.2015.187.


Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death.

Lee EA, Angka L, Rota SG, Hanlon T, Mitchell A, Hurren R, Wang XM, Gronda M, Boyaci E, Bojko B, Minden M, Sriskanthadevan S, Datti A, Wrana JL, Edginton A, Pawliszyn J, Joseph JW, Quadrilatero J, Schimmer AD, Spagnuolo PA.

Cancer Res. 2015 Jun 15;75(12):2478-88. doi: 10.1158/0008-5472.CAN-14-2676.


Inhibition of the Mitochondrial Protease ClpP as a Therapeutic Strategy for Human Acute Myeloid Leukemia.

Cole A, Wang Z, Coyaud E, Voisin V, Gronda M, Jitkova Y, Mattson R, Hurren R, Babovic S, Maclean N, Restall I, Wang X, Jeyaraju DV, Sukhai MA, Prabha S, Bashir S, Ramakrishnan A, Leung E, Qia YH, Zhang N, Combes KR, Ketela T, Lin F, Houry WA, Aman A, Al-Awar R, Zheng W, Wienholds E, Xu CJ, Dick J, Wang JC, Moffat J, Minden MD, Eaves CJ, Bader GD, Hao Z, Kornblau SM, Raught B, Schimmer AD.

Cancer Cell. 2015 Jun 8;27(6):864-76. doi: 10.1016/j.ccell.2015.05.004.


Mitochondrial Targeting of Doxorubicin Eliminates Nuclear Effects Associated with Cardiotoxicity.

Jean SR, Tulumello DV, Riganti C, Liyanage SU, Schimmer AD, Kelley SO.

ACS Chem Biol. 2015 Sep 18;10(9):2007-15. doi: 10.1021/acschembio.5b00268. Epub 2015 Jun 18.


Carnitine transporter CT2 (SLC22A16) is over-expressed in acute myeloid leukemia (AML) and target knockdown reduces growth and viability of AML cells.

Wu Y, Hurren R, MacLean N, Gronda M, Jitkova Y, Sukhai MA, Minden MD, Schimmer AD.

Apoptosis. 2015 Aug;20(8):1099-108. doi: 10.1007/s10495-015-1137-x.


Drug discovery in academia.

Shamas-Din A, Schimmer AD.

Exp Hematol. 2015 Aug;43(8):713-7. doi: 10.1016/j.exphem.2015.02.007. Epub 2015 Apr 23. Review.


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