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Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Chronic lymphocytic leukemia (CLL) is a cancer of the blood forming cells in the bone marrow resulting in an overproduction of B-lymphocytes that proliferate uncontrolled and crowd out normal cells. If chromosome 17 or the tumor suppressor gene 53 (TP53) bear mutations (e.g., 17p deletions; for a TP53 gene mutation analysis see Minervini et al., 2016) the prognosis is particularly poor. B-cell receptor (BCR) signaling is essential for normal B-cell development but also plays a major role in both B-cell-mediated autoimmune inflammation and B-cell malignancies (Puri et al., 2013). Inhibitors of this pathway targeting the spleen tyrosine kinase (Syk), Bruton’s tyrosine kinase (Btk), and phosphatidylinositol 3-kinase isoform p110delta (PI3Kδ) are promising treatment options. Examples are Ibrutinib as monotherapy and Idelalisib in combination with Rituximab (next scheme). These inhibitors promote apoptosis, inhibit proliferation, and also prevent CLL cells from responding to survival stimuli provided by the microenvironment. Idelalisib is a second-line drug for patients with relapsed CLL, and is also approved for the treatment of follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma. Ibrutinib acts by interacting with Bruton’s tyrosine kinase, whereas Idelalisib inhibits PI3Kδ (Pongas and Cheson, 2016; Greenwell et al., 2017; Barrientos, 2016). First direct in vivo measurements demonstrating inhibition of CLL cell proliferation and promotion of high rates of CLL cell death by ibrutinib have been reported by Burger et al. (2017).
Lymphocytes and Pulsing Magnetic Fields
Published in Andrew A. Marino, Modern Bioelectricity, 2020
Ruggero Cadossi, Giovanni Emilia, Giovanni Ceccherelli, Guiseppe Torelli
Chronic lymphocytic leukemia (CLL) is a pathological condition characterized by the presence in the patients’ peripheral blood of a large number of small lymphocytes (very often over 30,000/mm3), whose metabolic activity is poor. These are generally extremely homogeneous populations (90%). CLL lymphocytes often share the membrane antigens that are specific for B-lymphocytes and, much more rarely, for T-lymphocytes. It is therefore the B-lymphocyte populations that show an impaired response tD lectin stimulation (83,84). These characteristics make CLL lymphocytes very useful for lectin studies.
Construction and evaluation of wild and mutant ofatumumab scFvs against the human CD20 antigen
Published in Preparative Biochemistry & Biotechnology, 2023
Reza Maleki, Azam Rahimpour, Masoumeh Rajabibazl
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that develops from malignant B-lymphocyte clonal growth. In this malignancy, males are more likely to be affected than females and also it is known to be the most common leukemia in the Western regions among adults.[1]