Immune profiling after allogeneic hematopoietic cell transplantation in pediatric acute myeloid leukemia. Academic Article uri icon

Overview

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.

publication date

  • September 12, 2023

Research

keywords

  • Hematopoietic Stem Cell Transplantation
  • Leukemia, Myeloid, Acute

Identity

PubMed Central ID

  • PMC10471937

Scopus Document Identifier

  • 85171522727

Digital Object Identifier (DOI)

  • 10.1182/bloodadvances.2022009468

PubMed ID

  • 37327118

Additional Document Info

volume

  • 7

issue

  • 17