Immune Escape after Allogeneic Hematopoietic Cell Transplantation in Pediatric Acute Myeloid Leukemia.
Sanam ShahidNicholas CegliaJean-Benoît Le LuduecAndrew W McPhersonBarbara SpitzerTheodota KontopoulosViktoria BojilovaM Kazim PanjwaniMikhail RoshalSohrab P ShahOmar I Abdel-WahabBenjamin D GreenbaumKatharine C HsuPublished in: Blood advances (2023)
Although allogeneic hematopoietic cell transplantation (allo-HCT) is curative for high-risk pediatric acute myeloid leukemia (AML), disease relapse remains the primary cause of post-transplant mortality. To identify pressures imposed by allo-HCT on AML cells that escape the graft-versus-leukemia effect, we evaluated immune signatures at diagnosis and post-transplant relapse in bone marrow samples from four pediatric patients using a multimodal single-cell proteogenomic approach. Downregulation of MHC class II expression was most profound in progenitor-like blasts and accompanied by correlative changes in transcriptional regulation. Dysfunction of activated NK cells and CD8+ T-cell subsets at relapse was evidenced by loss of response to IFN-γ, TNF-α signaling via NF-kβ, and IL-2/STAT5 signaling. Clonotype analysis of post-transplant relapse samples revealed expansion of dysfunctional T cells and enrichment of T-regulatory and T-helper cells. Using novel computational methods, our results illustrate a diverse immune-related transcriptional signature in post-transplant relapses not previously reported in pediatric AML.
Keyphrases
- acute myeloid leukemia
- bone marrow
- cell cycle arrest
- induced apoptosis
- allogeneic hematopoietic stem cell transplantation
- single cell
- signaling pathway
- pi k akt
- stem cell transplantation
- free survival
- oxidative stress
- cell death
- cell proliferation
- immune response
- nk cells
- rheumatoid arthritis
- dendritic cells
- gene expression
- autism spectrum disorder
- mesenchymal stem cells
- high throughput
- cardiovascular events
- rna seq
- hematopoietic stem cell
- transcription factor
- type diabetes
- pain management
- poor prognosis
- prognostic factors
- low dose
- toll like receptor
- rectal cancer
- intellectual disability
- nuclear factor
- coronary artery disease
- cardiovascular disease
- long non coding rna
- lps induced
- peripheral blood