Faculty Opinions recommendation of Immune Escape of Relapsed AML Cells after Allogeneic Transplantation.
Year: 2019
Type: peer-review
Abstract: BACKGROUND-As consolidation therapy for acute myeloid leukemia (AML), allogeneic hematopoietic stem-cell transplantation provides a benefit in part by means of an immunemediated graft-versus-leukemia effect.We hypothesized that the immune-mediated selective pressure imposed by allogeneic transplantation may cause distinct patterns of tumor evolution in relapsed disease.METHODS-We performed enhanced exome sequencing on paired samples obtained at initial presentation with AML and at relapse from 15 patients who had a relapse after hematopoietic stem-cell transplantation (with transplants from an HLA-matched sibling, HLA-matched unrelated donor, or HLA-mismatched unrelated donor) and from 20 patients who had a relapse after chemotherapy.We performed RNA sequencing and flow cytometry on a subgroup of these samples and on additional samples for validation.RESULTS-On exome sequencing, the spectrum of gained and lost mutations observed with relapse after transplantation was similar to the spectrum observed with relapse after chemotherapy.Specifically, relapse after transplantation was not associated with the acquisition of previously unknown AML-specific mutations or structural variations in immune-related genes.In contrast,
Authors: Stephen Hunger, Jessica B Foster
Institution: Children's Hospital of Philadelphia
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4253768707