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

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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.

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Section
Commentaries
Author Biography

Neil S. Greenspan, Professor of Pathology at Case and the Director of the Histocompatibility and Immunogenetics Laboratory at University Hospitals Case Medical Center

Dr. Neil Greenspan received his A.B., magna cum laude, in Biochemical Sciences from Harvard College in 1975. He then earned M.D. and Ph.D. (Immunology) degrees at the University of Pennsylvania. From 1981 until 1986, Dr. Greenspan was a Resident in Laboratory Medicine (Clinical Pathology) at Barnes Hospital, and from 1982-1985 he was a Postdoctoral Fellow in Molecular Immunology at Washington University, both in St. Louis. In 1986, Dr. Greenspan became a faculty member at the Case School of Medicine. He is currently Professor of Pathology at Case and the Director of the Histocompatibility and Immunogenetics Laboratory at University Hospitals Case Medical Center.