Approved Research

Immunogenetics of clonal hematopoiesis of indeterminate potential: how human leukocyte antigen diversity influences clonal selection trajectories and risk of myeloid diseases in the general population

Lay summary

HLA (Human Leukocyte Antigen) genes are essential components of the immune system and represent the most variable (polymorphic) portion of the human genome. The variety (polymorphisms) of these genes allows the immune cells to efficiently fight against tumors and infections. However particular combinations of HLA genes have been suggested as able to predispose to the risk of solid cancers or autoimmune disorders.

"Clonal hematopoiesis of indeterminate potential" or CHIP is a condition commonly found in aged healthy subjects, characterized by aberrations (mutations) in genes important for the production of blood cells. This process may be in link with aging, cardiovascular diseases and in some cases may lead to malignant hematological diseases (including acute leukemias). Its prevalence rises with age and is about 10% among persons aged 70 to 80.

Our hypothesis is that HLA genes may have, as in solid cancers, an impact in determining this hematological condition and explain why some individuals might be more at risk than others.

With our clinical and translational expertise in immunology, hematology and computational biology we will study the associations between HLA and the occurrence of CHIP and linked diseases in all the individuals included in the UKbiobank, in order to identify patients at risk and improve their management strategies.

Given the prevalence of this disorder in the World Population, this research has the potential to be transformative for the Public Health.