Studying Chronic Lymphocytic Leukemia Microenvironment in the Multi Omics Era

In recent years, chronic lymphocytic leukemia (CLL) has undergone a radical change in the therapeutic landscape, allowing for the complete omission of chemotherapy in favor of targeted drugs. This reflects the improved understanding of the pathogenesis and biology of the disease, including both the genetic landscape of the leukemic clones and the crucial role of the numerous connections with the tumor microenvironment (TME). Regarding the latter, both in the bone marrow and in the lymph nodes, tissue architecture and function are reshaped by the lymphoid infiltrate to co-opt surrounding bystander cells, thereby supporting leukemic cell proliferation and survival. In this review, we explore the peculiarities of the CLL TME and how they translate into remarkable changes in the lymph nodal structure and in the inter-cellular interactions. We will elaborate on the potential that new multi-omics technologies might have in understanding the complex interplay occurring between CLL cells and TME.