Microenvironment interactions in chronic lymphocytic leukemia: a delicate equilibrium linking the quiescent and the proliferative pool

PALACIOS F; ABREU C; MORENO P; GIORDANO M; GAMBERALE R; OPPEZZO P

Chronic lymphocyti leukemia

Intech

Lugar: Rijeka; Año: 2012; p. 21 - 39

Chronic lymphocytic leukemic (CLL) is a B-cell tumor with monoclonal CD5pos B cells that proliferate and accumulate in peripheral lymphoid organs and bone marrow and flow into the peripheral blood. The proliferation of the leukemic clone takes place in  particular areas called proliferation centers or pseudofollicles where CLL cells are in close contact with activated T lymphocytes, stromal cells and/or other accessory cells. In this particular microenvironment CLL cells are endowed with the capacity to attract activated T cells and monocytes/macrophages, which in turn favor leukemic cell survival and proliferation leading to the progressive accumulation of the neoplastic cells. CLL cells present in peripheral blood are constantly nourished by an upstream proliferation cell compartment. We have described a proliferative subset in unmutated CLL patients characterized by the presence of active class switch recombination process and anomalous expression of the Activation Induced Cytidine Deaminase enzyme. This tumoral CLL subset expresses high levels of proliferation and antiapoptotic molecules, and appears to be a hallmark of a recent contact with an activated microenvironment. Of note, the presence of this proliferative pool in UN CLL patients is related to an aggressive course of the disease. Increasing number of observations indicate that most significant pathophysiological events in CLL occur in lymphoid tissues. A detailed and exhaustive study of the mechanism(s) whereby leukemic CLL B-cells respond to activating and proliferating signals from the microenvironment could provide important information about the biology of the leukemic clone and may help to design novel therapeutic strategies.