506 research outputs found
Glucocorticoids and tailored targeting of the unfolded protein response: searching for novel apoptosis inducing pathways in mature B-cell neoplasms
No full textOutcome and prognostic indicators in patients with haematological malignancies admitted to the Intensive Care Unit with life-threatening complications
No full textIn vitro apoptosis and clonal evolution in chronic lymphocytic leukemia : predictive value and possible influence on treatment
No full textCharacterization of the unfolded protein response by pharmacological agents in lymphoid malignancies
No full textNormal B cell development is tightly regulated by transcription factors and is characterized by the formation of the B-cell receptor. When the regulation and activation of B cell differentiation is disrupted, lymphomas and leukemias can occur. These lymphoid malignancies often resemble normal stages of the B cell differentiation. During normal B cell development a precursor B cell will ultimately form a terminal differentiated lymphocyte or plasma cell. These terminal differentiated B cells require massive increase in their biosynthetic capacity to synthesize thousands of antibodies per second for secretion. For this purpose, these cells rely on a highly developed endoplasmic reticulum (ER), the compartment where proteins are assembled and modified into functional antibodies. However, upon perturbations in ER function a stress response pathway can be activated, named the "unfolded protein response" (UPR). In the first place, the UPR is a cytoprotective signaling response and several studies have demonstrated already that activation of the UPR might have a crucial role in cancer. Until now, little is known about the role of the UPR in the germinal center (GC)-derived lymphomas since most investigations were performed on healthy B cells and multiple myeloma. Therefore, the initial aim of this doctoral work was to evaluate the expression levels of baseline and inducible UPR-related markers in DLBCL cell lines and in a plasma cell line.
Besides its protective role, the UPR may balance in the direction of cell death upon severe and prolonged stress. Manipulation of the UPR may be used as an alternative cell death mechanism since conventional treatments frequently activate the classical cell death pathways, like the intrinsic and extrinsic cell death program. Therefore, this cell death strategy is used on CLL patient samples. To accomplish this goal, the anticancer activities of two plant-derived compounds, xanthohumol (isolated from hop, Humulus lupulus L.) and withaferin A (isolated from Withania somnifera), were investigated.
In conclusion, our results provide a scientific basis for further investigations of the involvement of the UPR in DLBCL. Moreover, targeting the ER may be an interesting therapeutic strategy for CLL and other lymphoid malignancies, and for further development of new therapeutic agents
Risk mortality related to duration and severity of neutropenia following bone marrow transplantation
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The impact of the updated IMWG diagnostic criteria in a real-life SMM cohort : a single center experience
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