Distinct roles of hematopoietic cytokines in the regulation of leukemia stem cells in murine MLL-AF9 leukemia.

AML Bcl2 Mcl1 hematopoietic cytokines leukemia stem cells survival signaling

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
06 Dec 2023
Historique:
received: 10 08 2023
revised: 14 11 2023
accepted: 15 11 2023
medline: 16 12 2023
pubmed: 16 12 2023
entrez: 15 12 2023
Statut: aheadofprint

Résumé

Lymphoid-primed multipotent progenitor (LMPP)-like and granulocyte-monocyte progenitor (GMP)-like leukemia stem cells (LSCs) co-exist in the blood of most patients with acute myeloid leukemia (AML). Complete elimination of both types of LSCs is required to cure AML. Using an MLL-AF9-induced murine AML model, we studied the role of hematopoietic cytokines in the survival of LMPP- and GMP-like LSCs. We found that SCF or FLT3L promotes the survival of LMPP-like LSCs by stimulating Stat5-mediated Mcl1 expression, whereas interleukin-3 (IL-3) or IL-6 induces the survival of GMP-like LSCs by stimulating Stat3/nuclear factor κB (NF-κB)-mediated Bcl2 expression. Functional study demonstrated that, compared to AML cells cultured in IL-3 and IL-6 medium, AML cells in SCF- or Flt3L-only culture are highly clonogenic in in vitro culture and are highly leukemogenic in vivo. Our study suggests that co-inhibition of both STAT5-MCL1 and STAT3/NF-κB-BCL2 signaling might represent an improved treatment strategy against AML, specifically AML cases with a monocytic phenotype and/or FLT3 mutations.

Identifiants

DOI: 10.1016/j.stemcr.2023.11.003 PMID: 38101400
pubmed: 38101400
pii: S2213-6711(23)00452-6
doi: 10.1016/j.stemcr.2023.11.003
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Yanchun Li (Y)

Blood Disease Laboratory, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710126, P.R. China.

Christopher S Seet (CS)

Oncology Institute, Cardinal Bernardin Cancer Canter, Loyola University Medical Center, Maywood, IL 60153, USA; Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA.

Ryan Mack (R)

Oncology Institute, Cardinal Bernardin Cancer Canter, Loyola University Medical Center, Maywood, IL 60153, USA; Departments of Cancer Biology and Department of Radiation Oncology, Loyola University Medical Center, Maywood, IL 60153, USA.

Kanak Joshi (K)

Oncology Institute, Cardinal Bernardin Cancer Canter, Loyola University Medical Center, Maywood, IL 60153, USA; Departments of Cancer Biology and Department of Radiation Oncology, Loyola University Medical Center, Maywood, IL 60153, USA.

Austin P Runde (AP)

Oncology Institute, Cardinal Bernardin Cancer Canter, Loyola University Medical Center, Maywood, IL 60153, USA; Departments of Cancer Biology and Department of Radiation Oncology, Loyola University Medical Center, Maywood, IL 60153, USA.

Patrick A Hagen (PA)

Oncology Institute, Cardinal Bernardin Cancer Canter, Loyola University Medical Center, Maywood, IL 60153, USA; Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA.

Kevin Barton (K)

Oncology Institute, Cardinal Bernardin Cancer Canter, Loyola University Medical Center, Maywood, IL 60153, USA; Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA.

Peter Breslin (P)

Oncology Institute, Cardinal Bernardin Cancer Canter, Loyola University Medical Center, Maywood, IL 60153, USA; Departments of Biology, Molecular/Cellular Physiology, and Cancer Biology, Loyola University Medical Center, Maywood, IL 60153, USA.

Ameet Kini (A)

Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA.

Hong-Long Ji (HL)

Department of Surgery, Stritch School of Medicine, Loyola University Chicago Health Sciences Division, Maywood, IL 60153, USA; Burn and Shock Trauma Research Institute, Stritch School of Medicine, Loyola University Chicago Health Sciences Division, Maywood, IL 60153, USA.

Jiwang Zhang (J)

Oncology Institute, Cardinal Bernardin Cancer Canter, Loyola University Medical Center, Maywood, IL 60153, USA; Departments of Cancer Biology and Department of Radiation Oncology, Loyola University Medical Center, Maywood, IL 60153, USA; Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA. Electronic address: jzhang@luc.edu.

Classifications MeSH