CXCR4 Signaling Has a CXCL12-Independent Essential Role in Murine MLL-AF9-Driven Acute Myeloid Leukemia

Research output: Contribution to journalArticle


Acute myeloid leukemia (AML) is defined by an accumulation of immature myeloid blasts in the bone marrow. To identify key dependencies of AML stem cells in vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes in a syngeneic MLL-AF9 AML mouse model and show that CXCR4 is a top cell surface regulator of AML cell growth and survival. Deletion of Cxcr4 in AML cells eradicates leukemia cells in vivo without impairing their homing to the bone marrow. In contrast, the CXCR4 ligand CXCL12 is dispensable for leukemia development in recipient mice. Moreover, expression of mutated Cxcr4 variants reveals that CXCR4 signaling is essential for leukemia cells. Notably, loss of CXCR4 signaling in leukemia cells leads to oxidative stress and differentiation in vivo. Taken together, our results identify CXCR4 signaling as essential for AML stem cells by protecting them from differentiation independent of CXCL12 stimulation.


External organisations
  • University of Alabama
  • Skåne University Hospital
  • Brigham and Women's Hospital, Boston
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Hematology


  • acute myeloid leukemia, CRISPR, CXCL12, CXCR4, CXCR4 signaling, differentiation, leukemia stem cell, oxidative stress, ROS, screen
Original languageEnglish
Article number107684
JournalCell Reports
Issue number8
Publication statusPublished - 2020 May 26
Publication categoryResearch

Related research output

Ramprasad Ramakrishnan, 2020, Lund: Lund University, Faculty of Medicine. 86 p.

Research output: ThesisDoctoral Thesis (compilation)

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