Senescence as a key factor in leukemogenesis and bone marrow homeostasis in aging

Cancer is a major public health problem and one of the leading causes of death worldwide. In particular, it has been the second cause of death in Spain, Europe and United States. Although cancer can occur at any age, aging is one of the main risk factors for its development.

Aging is a complex scarcely understood multi-step process associated with the gradual functional decline of organs and systems.

In addition, age-dependent changes in epigenetic regulation occur, indicating that epigenetic regulation may also play an important role in aging. Similar changes have been observed at the cellular level in a mechanism known as senescence.

This mechanism is a cellular response that limits the proliferation of aged or damaged cells, behaving as a tumor suppressor mechanism and transformation events lead to escape from it.Chronic lymphocytic leukemia and acute myeloid leukemia are the most frequent types of leukemias and have median ages at diagnosis of 68-years.

Both have a low incidence in the young population and increase with age.

Thus, it is important to explore novel approaches to understand the mechanisms of aging favoring these types of leukemias, thereby unraveling new target molecules for treatment and prevention.

We propose to explore the senescence epigenetic profile in leukemic cells, the impact of senolytic drugs in patients and in the development of AML in spontaneous animal model.

The approach will bridge cancer epigenetics with senescence, aging and leukemogenesis.This proposal will augment my scientific knowledge and practical skills.

In addition, the complementary planned activities of the action will provide me to the additional tools to become an independent investigator in the near future.