Relapse Following Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia Apparently Due to Somatic Cell Evolution via Epigenetic Variation and Immune Selection

Neil S. Greenspan

Abstract


In this brief commentary, I discuss a recently published study that documents the role of immune escape in relapse of acute myeloid leukemia (AML) after hematopoietic cell transplantation (HCT). Of particular interest, the mechanism identified by the authors for the ability of the malignant cells to evade destruction by host T cells is the loss of cell surface expression of HLA class II molecules based on processes other than mutation. The authors labeled this mechanism for altered cell surface display of HLA class II antigens “epigenetic.” 

This study should be of strong interest for immunologists, oncologists and even specialists in infectious diseases for several reasons. First, the results extend the range of examples for which epigenetic mechanisms can play a critical role in resistance to therapy in oncology or infectious disease. Second, findings relating to decreased cell surface display of HLA class II molecules motivate investigation of novel approaches using cytokines to increase the numbers of HLA class II proteins on malignant myeloid cell membranes and reduce the extent of immune escape by these cells. Third, the data presented suggest experimental directions intended to clarify detailed molecular mechanisms underlying the cases of AML post-HCT relapse and raise questions relating to why some mechanisms of somatic cell evolution and not others are operative in different clinical settings.


Keywords


acute myeloid leukemia (AML); malignancy; blasts; allogeneic hematopoietic cell transplantation (HCT); chemotherapy; relapse; T cells; cytotoxicity; whole exome sequencing; mutation; epigenetic; HLA class II; HLA class I; interferon gamma; clone; subclone

Full Text:

HTML PDF

Refbacks

  • There are currently no refbacks.




Copyright (c) 2019 Neil S. Greenspan

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

© Pathogens and Immunity 2019

Case Western Reserve University; Division of Infectious Diseases

10900 Euclid Ave.; Mailstop 4984; Cleveland, OH 44106

(216) 368-6317; ISSN: 2469-2964; info@paijournal.com