Immune profiling after allogeneic hematopoietic cell transplantation in pediatric acute myeloid leukemia Journal Article
| Authors: | Shahid, S.; Ceglia, N.; Le Luduec, J. B.; McPherson, A.; Spitzer, B.; Kontopoulos, T.; Bojilova, V.; Panjwani, M. K.; Roshal, M.; Shah, S. P.; Abdel-Wahab, O.; Greenbaum, B.; Hsu, K. C. |
| Article Title: | Immune profiling after allogeneic hematopoietic cell transplantation in pediatric acute myeloid leukemia |
| Abstract: | Although allogeneic hematopoietic cell transplant (allo-HCT) is curative for high-risk pediatric acute myeloid leukemia (AML), disease relapse remains the primary cause of posttransplant 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 posttransplant relapse in bone marrow samples from4 pediatric patients using amultimodal single-cell proteogenomic approach. Downregulation of major histocompatibility complex class II expression was most profound in progenitor-like blasts and accompanied by correlative changes in transcriptional regulation. Dysfunction of activated natural killer cells and CD8+ T-cell subsets at relapse was evidenced by the loss of response to interferon gamma, tumor necrosis factor α signaling via NF-κB, and interleukin-2/STAT5 signaling. Clonotype analysis of posttransplant relapse samples revealed an 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 posttransplant relapses not previously reported in pediatric AML. © 2023 American Society of Hematology. All rights reserved. |
| Journal Title: | Blood Advances |
| Volume: | 7 |
| Issue: | 17 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2023-09-12 |
| Start Page: | 5069 |
| End Page: | 5081 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2022009468 |
| PUBMED: | 37327118 |
| PROVIDER: | scopus |
| PMCID: | PMC10471937 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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