1,993 research outputs found
EHA Endorsement of ESMO Clinical Practice Guidelines for Diagnosis, Treatment, and Follow-up of Chronic Lymphocytic Leukemia
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Modeling the Leukemia Microenviroment In Vitro
No full textOver the last decade, the active role of the microenvironment in the pathogenesis, development and drug resistance of B cell malignancies has been clearly established. It is known that the tissue microenvironment promotes proliferation and drug resistance of leukemic cells suggesting that successful treatments of B cell malignancies must target the leukemic cells within these compartments. However, the cross-talk occurring between cancer cells and the tissue microenvironment still needs to be fully elucidated. In solid tumors, this lack of knowledge has led to the development of new and more complex in vitro models able to successfully mimic the in vivo settings, while only a few simplified models are available for haematological cancers, commonly relying only on the co-culture with stabilized stromal cells and/or the addition of limited cocktails of cytokines. Here, we will review the known cellular and molecular interactions occurring between monoclonal B lymphocytes and their tissue microenvironment and the current literature describing innovative in vitro models developed in particular to study chronic lymphocytic leukemia (CLL). We will also elaborate on the possibility to further improve such systems based on the current knowledge of the key molecules/signals present in the microenvironment. In particular, we think that future models should be developed as 3D culture systems with a higher level of cellular and molecular complexity, to replicate microenvironmental-induced signaling. We believe that innovative 3D-models may therefore improve the knowledge on pathogenic mechanisms leading to the dissemination and homing of leukemia cells and consequently the identification of therapeutic targets
Ibrutinib in the real world patient: Many lights and some shades
No full textIbrutinib in the real world patient: many lights and some shades
Recensione del volume Multidisciplinarity in Audiovisual Translation (R. Agost, P. Orero, E. di Giovanni [a cura di.], 2012, MonTI 4).
No full textHS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses
No full textWe used a proteomic approach for identifying molecules involved in the pathogenesis of chronic lymphocytic leukemia (CLL). We investigated 14 patients who were completely concordant for IgV(H) mutational status (unmutated vs. mutated), CD38 expression (positive vs. negative), and clinical behavior (progressive vs. stable); these patients were characterized as having either poor or good prognoses. The 2 patient subsets differed in the expression of hematopoietic lineage cell-specific protein 1 (HS1). In patients with poor prognoses, most HS1 protein was constitutively phosphorylated, whereas only a fraction was phosphorylated in patients with good prognoses. This difference was investigated in a larger cohort of 26 unselected patients. The survival curve of all 40 patients analyzed revealed that patients with predominately phosphorylated HS1 experience a significantly shorter median survival time. As HS1 is a protein pivotal in the signal cascade triggered by B cell receptor (BCR) stimulation, we studied its pattern of expression following BCR engagement. Normal mature B cells stimulated by anti-IgM shifted the non- or less-phosphorylated form of HS1 toward the more phosphorylated form. Naive B cells showed both HS1 forms while memory B cells expressed mainly the phosphorylated fraction. These data indicate a central role for antigen stimulation in CLL and suggest a new therapeutic target for patients with aggressive disease
EU Cross-border Insolvency Proceedings
No full textThe author deals with the chapter's part concerning the applicable law and the cooperation regimes of the Regulation (EU) 2015/848. As regards the applicable law, the author pays particular attention to the exceptions to the general rule whereby the proceedings and the related effects are governed by lex concursus. As for the cooperation regime, the author deals mainly with the novelties concerning the group insolvency
Antigen receptor stereotypy in chronic lymphocytic leukemia
No full textThe discovery of almost identical or 'stereotyped' B-cell receptor immunoglobulins (BcR IG) among unrelated patients with chronic lymphocytic leukemia (CLL) cemented the idea of antigen selection in disease ontogeny and evolution. The systematic analysis of the stereotypy phenomenon in CLL revealed that around one-third of CLL patients may be grouped into subsets based on shared sequence motifs within the variable heavy complementarity determining region 3. Stereotyped subsets display a strikingly similar biology of the leukemic clones, referring to many different levels, from the immunogenetic and genetic and extending to the epigenetic and functional levels. Even more importantly, the homogeneity of stereotyped subsets has clinical consequences as patients assigned to the same stereotyped subset generally exhibit an overall similar disease course and outcome. In other words, stereotypy-based patient classification of CLL has already provided a more compartmentalized view of this otherwise heterogeneous disease and can assist in refining prognostication models. While this is relevant only for the one-third of cases expressing stereotyped BcR IG; in principle, however, the findings from further analysis of the stereotyped subsets may also contribute towards improved understanding of the remaining non-stereotyped fraction of CLL patients
Exploiting B-cell Receptor Stereotypy to Design Tailored Immunotherapy in Chronic Lymphocytic Leukemia
No full textData related to manuscript "Exploiting B-cell Receptor Stereotypy to Design Tailored Immunotherapy in Chronic Lymphocytic Leukemia" by Rovida A*, Maccalli C*, Scarfò L, Dellabona P, Stamatopoulos K, Ghia P. Clin Cancer Res. 2021 Feb 1;27(3):729-739. doi: 10.1158/1078-0432.CCR-20-1632. *Contributed equall
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