By Federico Caligaris-Cappio, Riccardo Dalla Favera
Chronic lymphocytic leukaemia (CLL) is the commonest leukaemia within the Western global. it's also the prototype of B-cell continual lymphoid malignancies and in their ramifications in the fields of hematology, immunology and oncology. For a long time the Cinderella of lymphoid malignancies CLL has now develop into the focal point of significant curiosity and more and more investigators from various components, together with genetics, molecular biology, simple and utilized immunology have gotten actively engaged within the research of CLL. Clinicians are contemplating CLL as a really fascinating goal of many initiatives which goal at translating the recent and fascinating advancements of uncomplicated technology into powerful new techniques to the sufferer.
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Consistently, many genes expressed in these cells mediate negatively regulating signals: cd72 (a negative regulator of B cell responsiveness), c-fes (negatively regulates macrophage activation), pac1 (dephosphorylates MAP-kinases), pirb1 (ITIM-containing inhibitory receptor), FCγRIIB (inhibitory coreceptor for the BCR), calcineurin (a Ca++ -dependent phosphatase), among others. Mature B cells, by contrast, are characterized by expression of many genes with activating functions, like annexin V, mapkkk88, tank, jak-2, and adenylyl-cyclase type VII.
The speciﬁc signatures established on puriﬁed cells could then be used to interrogate and successfully classify unpuriﬁed samples (Klein et al. 2001; Rosenwald et al. 2001). We believe that cellular contamination of the peripheral blood samples drawn from B-CLL patients, even if highly enriched for tumor cells, has a profound impact on the analysis of unpuriﬁed tumor cells, because B-CLL cells seem to contain low levels of mRNA. Do the IgV gene-mutated versus -unmutated gene expression proﬁles provide new information about those B-CLL subtypes?
Science 251:767–773 6. Ghia P, ten Boekel E, Rolink AG, Melchers F (1998) B-cell development: a comparison between mouse and man. Immunol Today 19:480–485 7. Ghia P, ten Boekel E, Sanz E, de la Hera A, Rolink A, Melchers F (1996) Ordering of human bone marrow B lymphocyte precursors by single-cell polymerase chain reaction analyses of the rearrangement status of the immunoglobulin H and L chain gene loci. J Exp Med 184:2217–2229 8. Grawunder U, Leu TM, Schatz DG, Werner A, Rolink AG, Melchers F, Winkler TH (1995) Down-regulation of RAG1 and RAG2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement.
Chronic Lymphocytic Leukemia by Federico Caligaris-Cappio, Riccardo Dalla Favera