Acute Myeloid Leukemia Alters Group 1 Innate Lymphoid Cell Differentiation from a Common Precursor
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Date
2021-04
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Abstract
Natural killer (NK) cells are known to be developmentally blocked and functionally inhibited in patients with acute myeloid leukemia (AML), resulting in poor clinical outcomes. Here we demonstrate that while NK cells are inhibited, closely related type 1 innate lymphoid cells (ILC1s) are enriched in the bone marrow of leukemic mice and in AML patients. Since NK cells and ILC1s share a common precursor (ILCP), we asked if AML acts on the ILCP to alter developmental potential. A combination of ex vivo and in vivo studies revealed that AML skewing of the ILCP towards ILC1s and away from NK cells represented a major mechanism of ILC1 generation. This process was driven by AML-mediated activation of the aryl-hydrocarbon receptor (AHR), a key transcription factor in ILCs, as inhibition of AHR led to decreased numbers of ILC1s and increased NK cells in the presence of AML. These results demonstrate a mechanism of ILC developmental skewing in AML and support further pre-clinical study of AHR inhibition in restoring normal NK cell development and function in the setting of AML.
Description
Health Sciences: 3rd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
Keywords
NK, ILC, AHR, AML