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Chronic lymphocytic leukemia (CLL) cells from clinically aggressive cases have a greater capacity to respond to external microenvironmental stimuli, including those transduced through Toll-like-receptor-9 (TLR9). Concomitant microRNA and gene expression profiling in purified CLL cells (n=17) expressing either unmutated (UM) or mutated (M) IGHV genes selected microRNAs from the miR-17∼92 family as significantly upregulated and in part responsible for modifications in the gene expression profile of UM CLL cells stimulated with the TLR9 agonist CpG. Notably, the stable and sustained upregulation of miR-17∼92 microRNAs by CpG was preceded by a transient induction of the proto-oncogene MYC. The enforced expression of miR-17, a major member from this family, reduced the expression of the tumor suppressor genes E2F5, TP53INP1, TRIM8 and ZBTB4, and protected cells from serum-free-induced apoptosis (P ≤ 0.05). Consistently, transfection with miR-17∼92 family antagomiRs reduced Bromo-deoxy-uridine incorporation in CpG-stimulated UM CLL cells. Finally, miR-17 expression levels, evaluated in 83 CLL samples, were significantly higher in UM (P=0.03) and ZAP-70(high) (P=0.02) cases. Altogether, these data reveal a role for microRNAs of the miR-17∼92 family in regulating pro-survival and growth-promoting responses of CLL cells to TLR9 triggering. Overall, targeting of this pathway may represent a novel therapeutic option for management of aggressive CLL. [ABSTRACT FROM AUTHOR]

The article presents the study on the Krüppel-like factor 2 transcription factor gene in splenic marginal zone lymphoma (SMZL). It discusses how the study was conducted which involved mutation analysis of Krüppel-like factor 2 transcription factor gene and of genes that regulate MZ B-cell differentiation. The results reportedly revealed that Krüppel-like factor 2 transcription factor gene is mutated in SMZL.

The article presents a study which examines the amount to circulate hemopoietic progenitors cells (HPC) in chronic lymphocytic leukemia (CLL) peripheral blood (PB) samples with various CD49d expression levels. Immunophenotpic characterization of HPC was done by examining the lineage-specific antigens' expression and surface molecules mediating cell-matrix and cell-cell interactions. The differences in the amount of circulating CD23+ cells were not discovered by comparing CLL cases.

Chronic lymphocytic leukemia (CLL) cells from clinically aggressive cases have a greater capacity to respond to external microenvironmental stimuli, including those transduced through Toll-like-receptor-9 (TLR9). Concomitant microRNA and gene expression profiling in purified CLL cells (n=17) expressing either unmutated (UM) or mutated (M) IGHV genes selected microRNAs from the miR-17∼92 family as significantly upregulated and in part responsible for modifications in the gene expression profile of UM CLL cells stimulated with the TLR9 agonist CpG. Notably, the stable and sustained upregulation of miR-17∼92 microRNAs by CpG was preceded by a transient induction of the proto-oncogene MYC. The enforced expression of miR-17, a major member from this family, reduced the expression of the tumor suppressor genes E2F5, TP53INP1, TRIM8 and ZBTB4, and protected cells from serum-free-induced apoptosis (P0.05). Consistently, transfection with miR-17∼92 family antagomiRs reduced Bromo-deoxy-uridine incorporation in CpG-stimulated UM CLL cells. Finally, miR-17 expression levels, evaluated in 83 CLL samples, were significantly higher in UM (P=0.03) and ZAP-70high (P=0.02) cases. Altogether, these data reveal a role for microRNAs of the miR-17∼92 family in regulating pro-survival and growth-promoting responses of CLL cells to TLR9 triggering. Overall, targeting of this pathway may represent a novel therapeutic option for management of aggressive CLL. [ABSTRACT FROM AUTHOR]

CD49d and CD38 are independent negative prognostic markers in chronic lymphocytic leukemia (CLL). Their associated expression marks a disease subset with a highly aggressive clinical course. Here, we demonstrate a constitutive physical association between the CD49d/CD29 integrin complex and CD38 in primary CLL cells and B-cell lines by (i) cocapping, (ii) coimmunoprecipitation and (iii) cell adhesion experiments using CD49d-specific substrates (vascular-cell adhesion molecule-1 or CS-1/H89 fibronectin fragments). The role of CD38 in CD49d-mediated cell adhesion was studied in CD49d+CD38+ and CD49d+CD38− primary CLL cells, and confirmed using CD38 transfectants of the originally CD49d+CD38− CLL-derived cell line Mec-1. Results indicate that CD49d+CD38+ cells adhered more efficiently onto CD49d-specific substrates than CD49d+CD38− cells (P<0.001). Upon adhesion, CD49d+CD38+ cells underwent distinctive changes in cell shape and morphology, with higher levels of phosphorylated Vav-1 than CD49d+CD38− cells (P=0.0006) and a more complex distribution of F-actin to the adhesion sites. Lastly, adherent CD49d+CD38+ cells were more resistant to serum-deprivation-induced (P<0.001) and spontaneous (P=0.03) apoptosis than the CD49d+CD38− counterpart. Altogether, our results point to a direct role for CD38 in enhancing CD49d-mediated adhesion processes in CLL, thus providing an explanation for the negative clinical impact exerted by these molecules when coexpressed in neoplastic cells. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "The expression levels of the pro-apoptotic XAF-1 gene modulate the cytotoxic response to Nutlin-3 in B chronic lymphocytic leukemia," published in a previous issue is presented.

A letter to the editor is presented about B-cell chronic lymphocytic leukemia that is published within the issue.

The article illustrates the relevance of CD49d as novel adverse prognosticator for B-cell chronic lymphocytic leukemia. Peripheral blood samples from 115 patients with ages 32-97 who were affected with the disease were used in the study while the distribution of clinical stage at diagnosis was based on Rai's criteria. According to the standard cut-off, mutated B-CLL have stronger survival rate than the unmutated cases. Result also showed that CD49d and CD 38 have adverse prognosticators in B-CLL.

Presents a letter to the editor on the mutational status of immunoglobulin genes in B-cell chronic lymphocytic leukemia and prognosis.

The article presents a reply by the authors to a study conducted by B. T. Pittner and colleagues on the correlation between the overexpression of CD38 and that of the integrin-α-chain CD49d. They contend that the same conclusion was reached in their recent study, in which the expression of surface antigens was analyzed. They added that they provided evidences on the clinical value of CD49d expression in B-CLL.

B-cell chronic lymphocytic leukemia (CLL), the most frequent leukemia in the Western world, is characterized by extremely variable clinical courses with survivals ranging from 1 to more than 15 years. The pathogenetic factors playing a key role in defining the biological features of CLL cells, hence eventually influencing the clinical aggressiveness of the disease, are here divided into "intrinsic factors", mainly genomic alterations of CLL cells, and "extrinsic factors", responsible for direct microenvironmental interactions of CLL cells; the latter group includes interactions of CLL cells occurring via the surface B cell receptor (BCR) and dependent to specific molecular features of the BCR itself and/or to the presence of the BCR-associated molecule ZAP-70, or via other non-BCR-dependent interactions, e.g. specific receptor/ligand interactions, such as CD38/CD31 or CD49d/VCAM-1. A putative final model, discussing the pathogenesis and the clinicobiological features of CLL in relationship of these factors, is also provided. [ABSTRACT FROM AUTHOR]