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

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

Epithelial maturation and molecular biology of oral HPV

Human papillomavirus (HPV) is widespread and can cause latent infection in basal cells, with low HPV DNA copy-number insufficient for transmission of infection; can cause subclinical infection that is active but without clinical signs; or can cause clinical infection leading to benign, potentially malignant or malignant lesions. The HPV cycle is influenced by the stage of maturation of the infected keratinocytes, and the production of virions is restricted to the post-mitotic suprabasal epithelial cells where all the virus genes are expressed

Genes, Heritability, ‘Race’, and Intelligence: Misapprehensions and Implications

The role of genetics in determining measured differences in mean IQ between putative racial groups has been a focus of intense discussion and disagreement for more than 50 years. While the last several decades of research have definitively demonstrated that genetic variation can influence measures of cognitive function, the inferences drawn by some participants in the controversy regarding the implications of these findings for racial differences in cognitive ability are highly dubious. Of equal importance, there is no compelling scientific rationale for focusing on and devoting substantial effort to determining mean differences in intelligence or other cognitive functions between groups with incompletely defined and dynamic (and therefore not definitively definable) boundaries

The Chemical Characterization of the Pneumococcal Transforming Principle

The editors of Pathogens and Immunity are commemorating this month, the 80th anniversary of the publication of the landmark article by Oswald Avery, Colin MacLeod, and Maclyn McCarty in the Journal of Experimental Medicine on February 1, 1944 [1]. The study by Avery et al determined with extraordinary rigor the chemical nature of the so-called transforming principle inferred to exist by Frederick Griffith based on experiments he published in 1928.

Ig constant region effects on variable region structure and function

The adaptive humoral immune response is responsible for the generation of antimicrobial proteins known as immunoglobulin molecules or antibodies. Immunoglobulins provide a defense system against pathogenic microbes and toxins by targeting them for removal and/or destruction. Historically, antibodies have been thought to be comprised of distinct structural domains known as the variable and constant regions that are responsible for antigen binding and mediating effector functions such as opsonization and complement activation, respectively. These domains were thought to be structurally and functionally independent. Recent work has revealed however, that in some families of antibodies, the two regions can influence each other. We will discuss the body of work that led to these observations, as well as the mechanisms that have been proposed to explain how these two different antibody regions may interact in the function of antigen binding