Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia

Shruti Bhatt; Marissa S. Pioso; Elyse Anne Olesinski; Binyam Yilma; Jeremy A. Ryan; Thelma Mashaka; Buon Leutz; Sophia Adamia; Haoling Zhu; Yanan Kuang; Abhishek Mogili; Abner J. Louissaint; Stephan R. Bohl; Annette S. Kim; Anita K. Mehta; Sneha Sanghavi; Youzhen Wang; Erick Morris; Ensar Halilovic; Cloud P. Paweletz; David M. Weinstock; Jacqueline S. Garcia; Anthony Letai

doi:10.1016/j.ccell.2020.10.010

Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia

Shruti Bhatt
, Marissa S. Pioso
, Elyse Anne Olesinski
, Binyam Yilma
, Jeremy A. Ryan
, Thelma Mashaka
, Buon Leutz
, Sophia Adamia
, Haoling Zhu
, Yanan Kuang
, Abhishek Mogili
, Abner J. Louissaint
, Stephan R. Bohl
, Annette S. Kim
, Anita K. Mehta
, Sneha Sanghavi
, Youzhen Wang
, Erick Morris
, Ensar Halilovic
, Cloud P. Paweletz

David M. Weinstock, Jacqueline S. Garcia, Anthony Letai

Research output: Contribution to journal › Article › peer-review

147 Scopus citations

Abstract

Bhatt et al. demonstrate that resistance to BCL-2 and MCL-1 antagonists emerges via selection for reduced mitochondrial apoptotic priming. Rapid measurements of drug-induced apoptotic signaling measured by dynamic BH3 profiling identify targeted agents with in vivo efficacy. BCL-2 and MCL-1 antagonist combinations overcome resistance to either single agent.

Original language	English
Pages (from-to)	872-890.e6
Journal	Cancer Cell
Volume	38
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2020.10.010
State	Published - 14 Dec 2020
Externally published	Yes

Keywords

BCL-2
BH3 mimetics
BH3 profiling
FLT-3
MCL-1
SMAC
leukemia
mitochondria
precision cancer medicine
venetoclax

Access to Document

10.1016/j.ccell.2020.10.010

Cite this

Bhatt, S., Pioso, M. S., Olesinski, E. A., Yilma, B., Ryan, J. A., Mashaka, T., Leutz, B., Adamia, S., Zhu, H., Kuang, Y., Mogili, A., Louissaint, A. J., Bohl, S. R., Kim, A. S., Mehta, A. K., Sanghavi, S., Wang, Y., Morris, E., Halilovic, E., ... Letai, A. (2020). Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia. Cancer Cell, 38(6), 872-890.e6. https://doi.org/10.1016/j.ccell.2020.10.010

@article{b7ce12612294430cb7356cec43063d63,

title = "Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia",

abstract = "Bhatt et al. demonstrate that resistance to BCL-2 and MCL-1 antagonists emerges via selection for reduced mitochondrial apoptotic priming. Rapid measurements of drug-induced apoptotic signaling measured by dynamic BH3 profiling identify targeted agents with in vivo efficacy. BCL-2 and MCL-1 antagonist combinations overcome resistance to either single agent.",

keywords = "BCL-2, BH3 mimetics, BH3 profiling, FLT-3, MCL-1, SMAC, leukemia, mitochondria, precision cancer medicine, venetoclax",

author = "Shruti Bhatt and Pioso, \{Marissa S.\} and Olesinski, \{Elyse Anne\} and Binyam Yilma and Ryan, \{Jeremy A.\} and Thelma Mashaka and Buon Leutz and Sophia Adamia and Haoling Zhu and Yanan Kuang and Abhishek Mogili and Louissaint, \{Abner J.\} and Bohl, \{Stephan R.\} and Kim, \{Annette S.\} and Mehta, \{Anita K.\} and Sneha Sanghavi and Youzhen Wang and Erick Morris and Ensar Halilovic and Paweletz, \{Cloud P.\} and Weinstock, \{David M.\} and Garcia, \{Jacqueline S.\} and Anthony Letai",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = dec,

day = "14",

doi = "10.1016/j.ccell.2020.10.010",

language = "English",

volume = "38",

pages = "872--890.e6",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

}

Bhatt, S, Pioso, MS, Olesinski, EA, Yilma, B, Ryan, JA, Mashaka, T, Leutz, B, Adamia, S, Zhu, H, Kuang, Y, Mogili, A, Louissaint, AJ, Bohl, SR, Kim, AS, Mehta, AK, Sanghavi, S, Wang, Y, Morris, E, Halilovic, E, Paweletz, CP, Weinstock, DM, Garcia, JS & Letai, A 2020, 'Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia', Cancer Cell, vol. 38, no. 6, pp. 872-890.e6. https://doi.org/10.1016/j.ccell.2020.10.010

TY - JOUR

T1 - Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia

AU - Bhatt, Shruti

AU - Pioso, Marissa S.

AU - Olesinski, Elyse Anne

AU - Yilma, Binyam

AU - Ryan, Jeremy A.

AU - Mashaka, Thelma

AU - Leutz, Buon

AU - Adamia, Sophia

AU - Zhu, Haoling

AU - Kuang, Yanan

AU - Mogili, Abhishek

AU - Louissaint, Abner J.

AU - Bohl, Stephan R.

AU - Kim, Annette S.

AU - Mehta, Anita K.

AU - Sanghavi, Sneha

AU - Wang, Youzhen

AU - Morris, Erick

AU - Halilovic, Ensar

AU - Paweletz, Cloud P.

AU - Weinstock, David M.

AU - Garcia, Jacqueline S.

AU - Letai, Anthony

PY - 2020/12/14

Y1 - 2020/12/14

N2 - Bhatt et al. demonstrate that resistance to BCL-2 and MCL-1 antagonists emerges via selection for reduced mitochondrial apoptotic priming. Rapid measurements of drug-induced apoptotic signaling measured by dynamic BH3 profiling identify targeted agents with in vivo efficacy. BCL-2 and MCL-1 antagonist combinations overcome resistance to either single agent.

AB - Bhatt et al. demonstrate that resistance to BCL-2 and MCL-1 antagonists emerges via selection for reduced mitochondrial apoptotic priming. Rapid measurements of drug-induced apoptotic signaling measured by dynamic BH3 profiling identify targeted agents with in vivo efficacy. BCL-2 and MCL-1 antagonist combinations overcome resistance to either single agent.

KW - BCL-2

KW - BH3 mimetics

KW - BH3 profiling

KW - FLT-3

KW - MCL-1

KW - SMAC

KW - leukemia

KW - mitochondria

KW - precision cancer medicine

KW - venetoclax

UR - https://www.scopus.com/pages/publications/85097436227

U2 - 10.1016/j.ccell.2020.10.010

DO - 10.1016/j.ccell.2020.10.010

M3 - Article

C2 - 33217342

AN - SCOPUS:85097436227

SN - 1535-6108

VL - 38

SP - 872-890.e6

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia

Abstract

Keywords

Access to Document

Fingerprint

Cite this