How the microenvironment shapes chronic lymphocytic leukemia: the cytoskeleton connection

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation in primary and secondary lymphoid tissues of CD5+ B cells that have the same B cell receptor (BCR) rearrangement. Genetic alterations and different stimuli originating from the microenvironment cooperate in the selection and expansion of the malignant clone. Molecular and functional analyses suggest that stimulation through the BCR affects the destiny of leukemic cells in terms of life or death. Microenvironmental signals are crucial for this process, inducing proliferation and leading to the survival and accumulation of leukemic cells within lymphoid organs. Nevertheless, a number of major biological issues still remain to be solved, including the relationships between cell proliferation and cell accumulation within lymphoid organs as well as the mechanisms that regulate CLL cell migration and recirculation between peripheral blood and lymphoid tissues. We focused on the role played by the cytoskeleton, given its relevance in controlling cellular shape, mobility, and homing. We hypothesize that hematopoietic cell-specific Lyn substrate 1 (HS1), a putative prognostic marker in CLL that interacts with distinct cytoskeleton adapters in leukemic B-lymphocytes, could regulate the CLL cell cytoskeleton.

Keywords:

• CLL
• Microenviroment
• Cytoskeleton

Acknowledgements

We thank all members of the Lymphoid Malignancies Unit for helpful suggestions and support.

Declaration of interest: The study was supported by the Associazione Italiana per la Ricerca sul Cancro – AIRC, Fondazione Italiana per la Ricerca sul Cancro – FIRC, ‘Fondazione Piera, Pietro e Giovanni Ferrero,’ EHA Fellowship Program, ‘CLLGRF – US/European Alliance for the Therapy of CLL,’ and Progetti Integrati Oncologia (PIO) – Ministero della Salute.