High Metabolic Dependence on Oxidative Phosphorylation Drives Sensitivity to Metformin Treatment in MLL/AF9 Acute Myeloid Leukemia

Longlong Liu; Pradeep Kumar Patnana; Xiaoqing Xie; Daria Frank; Subbaiah Chary Nimmagadda; Annegret Rosemann; Marie Liebmann; Luisa Klotz; Bertram Opalka; Cyrus Khandanpour

doi:10.3390/cancers14030486

High Metabolic Dependence on Oxidative Phosphorylation Drives Sensitivity to Metformin Treatment in MLL/AF9 Acute Myeloid Leukemia

Longlong Liu
, Pradeep Kumar Patnana
, Xiaoqing Xie
, Daria Frank
, Subbaiah Chary Nimmagadda
, Annegret Rosemann
, Marie Liebmann
, Luisa Klotz
, Bertram Opalka
, Cyrus Khandanpour^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Westfälische Wilhelms-Universität Münster
Universität Duisburg-Essen

26 Zitate (Scopus)

Abstract

Acute myeloid leukemia (AML) is a group of hematological cancers with metabolic heterogeneity. Oxidative phosphorylation (OXPHOS) has been reported to play an important role in the function of leukemic stem cells and chemotherapy-resistant cells and are associated with inferior prognosis in AML patients. However, the relationship between metabolic phenotype and genetic mutations are yet to be explored. In the present study, we demonstrate that AML cell lines have high metabolic heterogeneity, and AML cells with MLL/AF9 have upregulated mitochondrial activity and mainly depend on OXPHOS for energy production. Furthermore, we show that metformin repressed the proliferation of MLL/AF9 AML cells by inhibiting mitochondrial respiration. Together, this study demonstrates that AML cells with an MLL/AF9 genotype have a high dependency on OXPHOS and could be therapeutically targeted by metformin.

Originalsprache	Englisch
Aufsatznummer	486
Zeitschrift	Cancers
Jahrgang	14
Ausgabenummer	3
ISSN	2072-6694
DOIs	https://doi.org/10.3390/cancers14030486
Publikationsstatus	Veröffentlicht - 01.02.2022

Fördermittel

Funding: C.K. is supported partially by the Jose Carreras Leukaemia Foundation (DJCLS 17R/2018), by the Deutsche Krebshilfe (70112392), Deutsche Forschungsgemeinschaft (KH331/2-3), and the intramural funding of the Faculty of Medicine at University Hospital of Muenster (Kha2/002/20).

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Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Profilbereich: Lübeck Integrated Oncology Network (LION)
Zentren: Universitäres Cancer Center Schleswig-Holstein (UCCSH)

DFG-Fachsystematik

2.22-14 Hämatologie, Onkologie

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10.3390/cancers14030486

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title = "High Metabolic Dependence on Oxidative Phosphorylation Drives Sensitivity to Metformin Treatment in MLL/AF9 Acute Myeloid Leukemia",

abstract = "Acute myeloid leukemia (AML) is a group of hematological cancers with metabolic heterogeneity. Oxidative phosphorylation (OXPHOS) has been reported to play an important role in the function of leukemic stem cells and chemotherapy-resistant cells and are associated with inferior prognosis in AML patients. However, the relationship between metabolic phenotype and genetic mutations are yet to be explored. In the present study, we demonstrate that AML cell lines have high metabolic heterogeneity, and AML cells with MLL/AF9 have upregulated mitochondrial activity and mainly depend on OXPHOS for energy production. Furthermore, we show that metformin repressed the proliferation of MLL/AF9 AML cells by inhibiting mitochondrial respiration. Together, this study demonstrates that AML cells with an MLL/AF9 genotype have a high dependency on OXPHOS and could be therapeutically targeted by metformin.",

author = "Longlong Liu and Patnana, \{Pradeep Kumar\} and Xiaoqing Xie and Daria Frank and Nimmagadda, \{Subbaiah Chary\} and Annegret Rosemann and Marie Liebmann and Luisa Klotz and Bertram Opalka and Cyrus Khandanpour",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = feb,

day = "1",

doi = "10.3390/cancers14030486",

language = "English",

volume = "14",

journal = "Cancers",

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TY - JOUR

T1 - High Metabolic Dependence on Oxidative Phosphorylation Drives Sensitivity to Metformin Treatment in MLL/AF9 Acute Myeloid Leukemia

AU - Liu, Longlong

AU - Patnana, Pradeep Kumar

AU - Xie, Xiaoqing

AU - Frank, Daria

AU - Nimmagadda, Subbaiah Chary

AU - Rosemann, Annegret

AU - Liebmann, Marie

AU - Klotz, Luisa

AU - Opalka, Bertram

AU - Khandanpour, Cyrus

PY - 2022/2/1

Y1 - 2022/2/1

N2 - Acute myeloid leukemia (AML) is a group of hematological cancers with metabolic heterogeneity. Oxidative phosphorylation (OXPHOS) has been reported to play an important role in the function of leukemic stem cells and chemotherapy-resistant cells and are associated with inferior prognosis in AML patients. However, the relationship between metabolic phenotype and genetic mutations are yet to be explored. In the present study, we demonstrate that AML cell lines have high metabolic heterogeneity, and AML cells with MLL/AF9 have upregulated mitochondrial activity and mainly depend on OXPHOS for energy production. Furthermore, we show that metformin repressed the proliferation of MLL/AF9 AML cells by inhibiting mitochondrial respiration. Together, this study demonstrates that AML cells with an MLL/AF9 genotype have a high dependency on OXPHOS and could be therapeutically targeted by metformin.

AB - Acute myeloid leukemia (AML) is a group of hematological cancers with metabolic heterogeneity. Oxidative phosphorylation (OXPHOS) has been reported to play an important role in the function of leukemic stem cells and chemotherapy-resistant cells and are associated with inferior prognosis in AML patients. However, the relationship between metabolic phenotype and genetic mutations are yet to be explored. In the present study, we demonstrate that AML cell lines have high metabolic heterogeneity, and AML cells with MLL/AF9 have upregulated mitochondrial activity and mainly depend on OXPHOS for energy production. Furthermore, we show that metformin repressed the proliferation of MLL/AF9 AML cells by inhibiting mitochondrial respiration. Together, this study demonstrates that AML cells with an MLL/AF9 genotype have a high dependency on OXPHOS and could be therapeutically targeted by metformin.

UR - https://www.scopus.com/pages/publications/85122878972

U2 - 10.3390/cancers14030486

DO - 10.3390/cancers14030486

M3 - Journal articles

AN - SCOPUS:85122878972

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 3

M1 - 486

ER -

High Metabolic Dependence on Oxidative Phosphorylation Drives Sensitivity to Metformin Treatment in MLL/AF9 Acute Myeloid Leukemia

Abstract

Fördermittel

UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

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