Many cellular processes converge on the proteasome, and its key regulatory role is increasingly being recognized. Proteasome inhibition allows the manipulation of many cellular pathways including apoptotic and cell cycle mechanisms. The proteasome inhibitor bortezomib has enhanced responses in newly diagnosed patients with myeloma and provides a new line of therapy in relapsed and refractory patients. Malignant cells are more sensitive to proteasome inhibition than normal haematopoietic cells. Proteasome inhibition enhances many conventional therapies and its role in leukaemia is promising.
Berenson JR, Anderson KC, Audell RA, et al. Monoclonal gammopathy of undetermined significance: a consensus statement. Br J Haematol 2010;150:28e38.Paraproteins are common in the elderly population and less than 1% per year will transform to a more serious B cell malignancy. In light of the low transformation rate, afflicted patients do not need to be referred to a haematologist. Rather, this guideline provides advice on the diagnosis, staging and follow-up of monoclonal gammopathy of undetermined significance, and raises awareness of the associated problems of peripheral neuropathy, thromboembolic disease and osteoporosis.Coiffier B, Losic N, Ronn BB, et al. Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1e2 study. Br J Haematol 2010;150:58e71.Rituximab is a monoclonal antibody to the CD20 transmembrane protein, and it has significantly improved outcomes in many B cell lymphoproliferative disorders. Ofatumumab is a new anti-CD20 monoclonal antibody that induces apoptosis through complement activation and antibody-dependent cell-mediated cytotoxicity. Ofatumumab can induce responses in rituximab-resistant patients. In this phase 2 trial of 37 patients with CLL, efficacy was inversely proportional to body size and clearance. Ofatumumab was detectable in the serum 7 months after the last high-dose infusion.Greenberg PL. Current therapeutic approaches for patients with myelodysplastic syndromes. Br J Haematol 2010;150:131e43.Myelodysplasia and leukaemia are at opposite ends of a spectrum of haematopoietic dysfunction affecting proliferation and differentiation. Myelodysplasia can be stratified into high risk and low risk depending on the blast percentage, cytogenetic abnormalities and number of cytopenias. Management ranges from observation to intensive chemotherapies. The indications for lenalidomide, granulocyte colony-stimulating factor and erythropoietin and their outcomes in low risk patients are discussed. Immunosuppressive therapy is recommended in younger patients with hypoplastic marrows. Azacitabine and dacitabine are of benefit in older patients with high-risk disease, for whom intensive chemotherapy is contraindicated. Management flow charts are provided.
Snippets in pathologySobrinho-Simões M, Wilczek V, Score J, et al. In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular Snippets in pathology
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.