Diane Jelinek

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..Identification of these mechanisms may allow development of agents that are more universally effective than IFN-alpha...

..Finally, we identified a group of 31 genes that distinguish between low (Rai stage 0) and high (Rai stage 4) risk patients, suggesting that there may also be a gene expression signature that associates with disease progression...

..Expression of BCMA, TACI, and BAFF-R by MM taken together with the ability of BLyS to support MM cell growth and survival has exciting implications because they may be potential therapeutic targets...

..These data strongly encourage the study of these biological markers as they relate to disease heterogeneity in B-CLL...

..In this article, we will review the spectrum of human B lineage malignancies and discuss current evidence supporting a role for BLyS and APRIL in fueling the growth and survival of specific B cell malignancies...

..In summary, these studies suggest that IGFs may play an important role in multiple myeloma by virtue of their ability to directly stimulate tumor cell growth as well as modulate the magnitude of IL-6-driven growth...

..Importantly, this interaction has not been noted in studies utilizing the same gp130 chimeric receptor system in non-MM cells...

..This combined approach has the potential to assess the relative importance of several signalling events in myeloma cell growth control and identify IL-6 responsive genes in this malignancy...

..These results therefore provide a previously unrecognized molecular mechanism for the immunosuppressive properties of thiopurine antimetabolite drugs...

..No complete or partial remissions were observed. Individually and collectively, these studies indicate that single-agent anti-VEGF therapy has minimal clinical activity for patients with relapsed/refractory CLL...

..We conclude that inhibition of survivin expression is an attractive therapeutic strategy in aggressive non-Hodgkin's lymphomas, and that combining survivin ASO with rituximab may enhance the efficacy of this approach...

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..Thus, a VEGF-VEGF receptor pathway in CLL B cells can be linked to activation of STAT proteins that are able to enhance their apoptotic resistance...

..The remaining 20% are characterised by absence of IgH expression; we aimed to assess prevalence of a corresponding precursor entity, light-chain MGUS...

..The sharpened images look like a set of donuts, which concurs with our knowledge of the spotting process. Oversharpened images are actually useful as well, in locating the centers of each spot...

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..Taken together, these data suggest that CD38 is a marker of a more recently activated CLL B cell. This in turn may explain the biological and clinical differences between CD38-positive type B-CLL and CD38-negative type B-CLL...

..These results provide new insight into normal human B-cell biology as well as provide clues about the transformed cell in B-CLL...

..This finding provides a strong rationale for the investigation of cellular immunotherapy in B-cell NHL...

..Thus, our studies illustrate the striking dependence of dsRNA-mediated gene silencing in some cells on the methods of dsRNA transfection...

..199) were noted with lower TCL-1 expression. These data suggest TCL-1 expression may help predict treatment outcome in CLL patients following chemoimmunotherapy, and examination in larger studies is warranted...

..001). The percentage of smudge cells as a continuous variable correlated with overall survival (P=.04). The estimation of smudge cells on a blood smear could be a universally available prognostic test in early-stage CLL...

..These findings have important implications for both clinical management and trials of early treatment for patients with high-risk, early-stage CLL...

..Prognostic factors for the progression and outcome of this disease are unclear...

..Taken together, these data define a complex role for BAFF in humoral immune responses and show for the first time that BAFF can also play an inhibitory role in B cell differentiation...

..The serum immunoglobulin FLC ratio is an important additional determinant of clinical outcome in patients with SMM...

..In this phase 2 study, the authors tested the safety and efficacy of early treatment for patients with high-risk CLL using alemtuzumab and rituximab...

..Moreover, these cell lines will provide an invaluable tool to better understand AL, from the combined perspectives of amyloidogenic protein structure and amyloid formation, genetics, and cell biology...

..These characteristics can be modified and continued evaluation of immunomodulatory drugs, vaccination strategies and cellular therapies to delay/prevent disease progression are warranted...

..Revisions of the National Cancer Institute Working Group 96 criteria should consider the aetiology of cytopenia in staging CLL patients...

..Importantly, anti-CD49d antibodies are already approved for treatment of other human diseases. Clinical testing of anti-CD49d therapy in CLL appears warranted...

..In contrast, CD38 predicted TTT (p=0.02) regardless of the proposed new classification. Molecular characteristics of the leukemic clone are a better predictor of progression than an arbitrary ALC or B lymphocyte count threshold...

..In addition, these data support the concept that antigen-driven selection of specific Ig receptors plays a role in the clinical course of B-CLL...

..Collectively, our data suggest that the BBR profile may serve as a footprint of the activation history and stage of differentiation of normal human B cells...

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..Moreover, this study may explain more clearly why high BLyS production is often correlated with certain inflammatory autoimmune diseases and B-lymphocyte malignancies...

..These findings validate our previous report of ErbB3 involvement in IFN-alpha-induced proliferation and further suggest that both Janus kinase members, Tyk2 and Jak1, play a role in the transactivation of ErbB3 in this model system...

..These data suggest that increased IL-3 levels in the bone marrow microenvironment of MM patients with imbalanced AML-1A and AML-1B expression can increase bone destruction and tumor cell growth...

..These results suggest that ErbB3 expression alone does not uniquely confer IFN-alpha growth responsiveness, but instead may amplify proliferation rates in MM cells that have acquired atypical expression of this receptor...

..Importantly, only CD38+ was significantly associated with high-risk FISH categories (+12, 11q- and 17p-) after adjustment for the effects of other variables...

..Finally, transactivation of gp130 may be a common theme in myeloma cells, perhaps providing a mechanism for enhanced or qualitatively distinct cellular responses to specific stimuli...

..The data suggest that strategies that enhance AML-1B expression or decrease AML-1A in MM cells may be beneficial therapeutically...

..Because these molecules are key regulators of B-cell homeostasis and tumor progression, leukemic cell autocrine expression of BLyS and APRIL may be playing an important role in the pathogenesis of this disease...

..These data suggest that IL-12 and rituximab is an active combination and further studies of this combination in B-cell non-Hodgkin lymphoma are warranted...

..Thus, these results suggest that VEGF signaling regulates survival signals in CLL cells and that interruption of this autocrine pathway results in caspase activation and subsequent leukemic cell death...

..In summary, we found that BLyS and its receptors represent a potentially important therapeutic target in B-cell lymphoma...

..Deletions in IGHv occurred in 25% of patients and correlated with IGHv gene expression. Probes for 6q23 detected more deletions in 6q than probes for 6q21...

..Thus, IL6 and its downstream signaling may be of biologic importance in WM. Further elucidation of the role of IL-6 in WM is warranted as this may offer a potential therapeutic avenue...

..6-fold increase in activity (P = .004). CONCLUSION: Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter...

..These results demonstrate that stable isotope labeling and mass spectrometry can complement 2D gel electrophoresis and gene microarray technologies for identifying putative and perhaps unique prognostic markers in CLL...

..These studies suggest that the IL-4R, on B-CLL cells, can serve as a unique molecular target for directing cytotoxic agents in the therapy of B-CLL...

..We show that despite the variance in SCX, capillary LC, and the data-dependent selection of precursor ions, an overlap of 64% between proteins identified in replicate runs was achieved for this system...

..Several chemokine receptors (CCR1, CCR5, and CCR9) mediate the effects of MIP-1alpha. In this study, we determined which of these mediates the effects of MIP-1alpha on human OCL formation and myeloma cells...

..Collectively, our data suggest that BLyS may modulate adaptive immune cells indirectly by inducing DC maturation...

..1), and p53 mutations have been reported to predict the clinical course and overall survival of patients with chronic lymphocytic leukemia (CLL). In addition, ZAP-70 and Bcl-2 family proteins have been explored as predictors of outcome...

..Three-year survival was 41% (95% CI: 26 - 66%). HDMP-rituximab is an active regimen in patients with relapsed, refractory, and cytogenetically high-risk CLL. Further evaluation of this regimen in controlled trials appears warranted...

..Physicians should strictly adhere to established criteria to initiate treatment for CLL patients who are not participating in clinical trials...

..Through these studies, we aim to add novel insight into the etiology of this disease and are optimistic that this information can be used to devise timely novel therapeutic interventions. ..

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..Through these studies, we aim to add novel insight into the etiology of this disease and are optimistic that this information can be used to devise timely novel therapeutic interventions. ..