Inflammatory bone marrow signaling in pediatric acute myeloid leukemia distinguishes patients with poor outcomes

Hamid Bolouri (), Rhonda E. Ries, Alice E. Wiedeman, Tiffany Hylkema, Sheila Scheiding, Vivian H. Gersuk, Kimberly O’Brien, Quynh-Anh Nguyen, Jenny L. Smith, S. Alice Long and Soheil Meshinchi ()
Additional contact information
Hamid Bolouri: Benaroya Research Institute
Rhonda E. Ries: Fred Hutchinson Cancer Research Center
Alice E. Wiedeman: Benaroya Research Institute
Tiffany Hylkema: Fred Hutchinson Cancer Research Center
Sheila Scheiding: Benaroya Research Institute
Vivian H. Gersuk: Benaroya Research Institute
Kimberly O’Brien: Benaroya Research Institute
Quynh-Anh Nguyen: Benaroya Research Institute
Jenny L. Smith: Fred Hutchinson Cancer Research Center
S. Alice Long: Benaroya Research Institute
Soheil Meshinchi: Fred Hutchinson Cancer Research Center

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract High levels of the inflammatory cytokine IL-6 in the bone marrow are associated with poor outcomes in pediatric acute myeloid leukemia (pAML), but its etiology remains unknown. Using RNA-seq data from pre-treatment bone marrows of 1489 children with pAML, we show that > 20% of patients have concurrent IL-6, IL-1, IFNα/β, and TNFα signaling activity and poorer outcomes. Targeted sequencing of pre-treatment bone marrow samples from affected patients (n = 181) revealed 5 highly recurrent patterns of somatic mutation. Using differential expression analyses of the most common genomic subtypes (~60% of total), we identify high expression of multiple potential drivers of inflammation-related treatment resistance. Regardless of genomic subtype, we show that JAK1/2 inhibition reduces receptor-mediated inflammatory signaling by leukemic cells in-vitro. The large number of high-risk pAML genomic subtypes presents an obstacle to the development of mutation-specific therapies. Our findings suggest that therapies targeting inflammatory signaling may be effective across multiple genomic subtypes of pAML.

Date: 2022
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34965-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34965-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34965-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().