Dissemin is shutting down on January 1st, 2025

Published in

American Society of Hematology, Blood Advances, 17(7), p. 5069-5081, 2023

DOI: 10.1182/bloodadvances.2022009468

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Immune profiling after allogeneic hematopoietic cell transplantation in pediatric acute myeloid leukemia

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

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 from 4 pediatric patients using a multimodal 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.