MOLECULAR PATHWAYS IN LOW-GRADE B-CELL LYMPHOMA

Low grade B-cell non-Hodgkin's lymphomas (B-NHL) represent a markedly heterogeneous group of lymphoproliferative disorders, including B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CCL/SLL), lymphoplasmacytoid lymphoma (LPL), follicular lymphoma (FL), mucosa-as sociated lymphoid tissue lymphoma (MALTL), and splenic lymphoma with v illous lymphocytes (SLVL). The molecular pathogenesis of low grade B-N HL is characterized by distinct genetic pathways which selectively ass ociate with each clinicopathologic category. At diagnosis, B-CLL/SLL f requently display deletions of 13q14 and trisomy 12, whereas evolution to Richter's syndrome associates with disruption of p53. LPL carries t(9;14)(p13;q32) in 40-50% of the cases, leading to the deregulated ex pression of the PAX-5 gene. FL consistently harbors rearrangements of BCL-2 independent of the cytologic variant. With time, a fraction of F L cases accumulates mutations of p53 and evolves into a high grade B-N HL. Low grade MALTL are characterized by the frequent occurrence of tr isomy 3 and, occasionally, by p53 mutations. SLVL carries p53 mutation s in a fraction of cases. The identification of distinct genetic categ ories among low grade B-NHL may help in the therapeutic stratification of these disorders. In addition, genetic lesions of low grade B-NHL h ave proved to be a useful molecular marker for monitoring minimal resi dual disease.