Small Lymphocytic Lymphoma and Chronic Lymphocytic Leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world, characterized by peripheral blood B-cell lymphocytosis as well as lymphadenopathy, organomegaly, cytopenias, and systemic symptoms. Chronic lymphocytic leukemia cells have a distinctive immunophenotype, and the disease has a characteristic pattern of histological infiltration in the lymph node and bone marrow. The clinical course of CLL is heterogeneous, with some patients presenting with very indolent disease and other patients having a more aggressive malignancy. It is known that genetic abnormalities underlie this difference in clinical presentation. Some patients may present solely with lymphadenopathy, organomegaly, and presence of infiltrating monoclonal B cells with the same immunophenotype as CLL cells, but lacking peripheral blood lymphocytosis. This disease is called small lymphocytic lymphoma (SLL) and has been considered for almost 2 decades to be the tissue equivalent of CLL. Both CLL and SLL are currently considered different manifestations of the same entity by the fourth edition of the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. It is suspected that differential expression of chemokine receptors (e.g., reduced expression of R1 and CCR3 in SLL cells), integrins (e.g., CLL cells have lower expression of integrin αLβ2), and genetic abnormalities (a higher incidence of trisomy 12 and lower incidence of del(13q) is found in SLL) may explain some of the clinical differences between these 2 disorders. However, there is still a lack of knowledge on the precise biological basis underlying the different clinical presentations of CLL and SLL. It is expected that future studies will shed light on the pathophysiology of both disorders.

Trisomy 12 chronic lymphocytic leukemia cells exhibit upregulation of integrin signaling that is modulated by NOTCH1 mutations

“…1,2 Although trisomy 12 is present in approximately 16% of cases of CLL, the prevalence of this cytogenetic abnormality is significantly higher in small lymphocytic lymphoma (SLL) where it is present in 28% of cases. 3 Furthermore, acquisition of trisomy 12 also has been recently implicated in a third of cases of Richter's transformation. 4 The increased prevalence of trisomy 12 in these lymphomas is of particular interest in light of studies reporting increased expression of the a-integrins CD11a and CD49d on trisomy 12 CLL cells.…”

NK cell dysfunction in chronic lymphocytic leukemia is associated with loss of the mature cells expressing inhibitory killer cell Ig-like receptors

“…4 SLL patients present with monoclonal B cells that predominantly infiltrate tissues, especially lymph nodes, bone marrow, and spleen, instead of circulating in peripheral blood. This distinct localization of SLL and CLL appears to result from their differential expression of chemokine receptors and/or adhesion molecules.…”

Quantitative real time PCR analysis of apoptotic gene expression in chronic lymphocytic leukemia patients and their relationships with chemosensitivity

“…Expression of p53 gene was lower in CLL and CLL/ SLL compared to the control group, however, the difference was not statistically significant. Similarly, Santos et al [29] reported that both CLL and CLL/SLL are currently considered different manifestations of the same entity in the fourth edition of the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. It is suspected that differential expression of chemokine receptors (e.g., reduced expression of R1 and CCR3 in SLL cells), integrins (e.g., CLL cells have lower expression of integrin αLβ2), and genetic abnormalities (a higher incidence of trisomy 12 and lower incidence of del(13q) is found in CLL/SLL) may explain some of the clinical differences between these two disorders [29].…”