Stromal cell-mediated glycolytic switch in CLL cells involves Notch-c-Myc signaling.

Blood
Regina JitschinDimitrios Mougiakakos

Abstract

It is well established that the stromal niche exerts a protective effect on chronic lymphocytic leukemia (CLL) cells, thereby also affecting their drug sensitivity. One hallmark of malignant cells is metabolic reprogramming, which is mostly represented by a glycolytic shift known as the Warburg effect. Because treatment resistance can be linked to metabolic alterations, we investigated whether bone marrow stromal cells impact the bioenergetics of primary CLL cells. In fact, stromal contact led to an increase of aerobic glycolysis and the cells' overall glycolytic capacity accompanied by an increased glucose uptake, expression of glucose transporter, and glycolytic enzymes. Activation of Notch signaling and of its direct transcriptional target c-Myc contributed to this metabolic switch. Based on these observations, CLL cells' acquired increased glucose dependency as well as Notch-c-Myc signaling could be therapeutically exploited in an effort to overcome stroma-mediated drug resistance.

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Citations

Feb 4, 2016·European Journal of Nutrition·Delphine CasabonneSilvia de Sanjose
Oct 16, 2016·Best Practice & Research. Clinical Haematology·Michael Y ChoiDeepak Kumar
Dec 14, 2016·Annual Review of Pathology·Jon C AsterStephen C Blacklow
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Nov 25, 2017·British Journal of Haematology·Markus SchickUlrich Keller
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Feb 15, 2020·Cells·Simone MirabiliiAgostino Tafuri
Sep 23, 2018·Nature Communications·Maurizio MangoliniIngo Ringshausen
Apr 1, 2019·Cancer Reports·Travis NemkovJulie A Reisz
Jul 13, 2018·Frontiers in Oncology·Emanuela RosatiPaolo Sportoletti
Dec 12, 2018·Frontiers in Oncology·Francesca ArrugaSilvia Deaglio
Dec 1, 2020·Frontiers in Oncology·Martin BöttcherDimitrios Mougiakakos
May 2, 2021·Journal for Immunotherapy of Cancer·Martin BöttcherDimitrios Mougiakakos
May 18, 2021·Leukemia & Lymphoma·Sarah HandlGloria Lutzny-Geier
Dec 24, 2020·Blood Reviews·Binyan XuYuhua Li
Jul 25, 2021·Cancers·Dimitra MavridouMichalis Aivaliotis

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