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-associated lymphoid tissue lymphoma (MALTL), and splenic lymphoma with villous lymphocytes (SLVL). The molecular pathogenesis of low grade B-NHL is characterized by distinct genetic pathways which selectively associate with each clinicopathologic category. At diagnosis, B-CLL/SLL frequently 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 expression of the PAX-5 gene. FL consistently harbors rearrangements of BCL-2 independent of the cytologic variant. With time, a fraction of FL cases accumulates mutations of p53 and evolves into a high grade B-NHL. Low grade MALTL are characterized by the frequent occurrence of trisomy 3 and, occasionally, by p53 mutations. SLVL carries p53 mutations in a fraction of cases. The identification of distinct genetic categories among low grade B-NHL may help in the therapeutic stratification of these disorders. In addition, genetic lesions of low grade B-NHL have proved to be a useful molecular marker for monitoring minimal residual disease.
Gaidano
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Dipartimento di Scienze Biomediche e Oncologia Umana, Ospedale San Luigi, Università di Torino, Orbassano-Torino, Italy.
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Capello
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Cilli
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D015703:Antigens, CD / Q000032:analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics; D008224:Lymphoma, Follicular / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics
D015703:Antigens, CD; D004273:DNA, Neoplasm