title: Hairy cell leukemia-new genes, new targets.
abstract: Hairy cell leukemia (HCL), a B cell malignancy comprising 2 % of all leukemias, has become quite exciting recently with regard to the development of new targets for therapy. This review will focus on advancements made within the past 1-2 years in targeted therapy for this disease. These advances may be grouped into two very difference categories, namely targeting of CD22 with the recombinant immunotoxin moxetumomab pasudotox, and targeting of the mutated BRAF component of the MAP kinase pathway. Moxetumomab pasudotox in phase I testing was recently reported to be associated with an overall response rate of 86 % and a complete remission (CR) rate of 46 % in 28 patients with relapsed and refractory HCL. Many of the CRs are without minimal residual disease (MRD). Severe or dose limiting toxicity was not observed on this trial, but a completely reversible and largely asymptomatic form of grade 2 hemolytic uremic syndrome occurred in two patients during retreatment. This agent has commenced phase III multicenter testing to validate its phase I results. An extensive number of studies have documented the V600E mutation in nearly all HCL patients, but not in similar hematologic malignancies. The thymidine kinase inhibitor vemurafenib, which inhibits the V600E mutant of BRAF, was reported to induce a CR in multiply relapsed and refractory HCL, with nearly complete clearing of MRD. One additional partial and one additional complete remission were subsequently reported.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. kreitmar@mail.nih.gov
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
mesh_terms: D001427:Bacterial Toxins / Q000276:immunology / Q000627:therapeutic use; D005098:Exotoxins; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D007211:Indoles; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D013449:Sulfonamides; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors; D000077484:Vemurafenib
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C541974:immunotoxin HA22; D013937:Thymidine Kinase; D048493:Proto-Oncogene Proteins B-raf
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