title: Monoclonal B-cell lymphocytosis: right track or red herring?
abstract: Monoclonal B-cell lymphocytosis (MBL), a newly recognized entity found in approximately 3% of normal persons, precedes chronic lymphocytic leukemia. However, MBLs progress into overt malignancy only in a very minor portion of cases, thus raising the clinical concern of whether and how we can discriminate at diagnosis which rare cases will evolve into a fully fledged tumor. Understanding the molecular/biologic features underlying the risk of progression may significantly modify our strategies for correctly managing B-cell premalignant states. MBL cells bear the same chromosomal abnormalities of chronic lymphocytic leukemia. Genome-wide sequencing and animal models indicate that genetic abnormalities disrupting the control of cell growth and survival cooperate with microenvironment-triggered events, mainly represented by antigen-mediated B-cell receptor and coreceptor stimulation, to trigger and fuel clonal expansion. The initial functional activation of survival/proliferation pathways may later become subsidized by autonomous genetic abnormalities (eg, a single mutation) affecting the same or parallel critical signaling pathway(s).
authors.affiliation: Laboratory of B Cell Neoplasia, Division of Molecular Oncology, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy. ghia.paolo@hsr.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.forename: Federico
authors.initials: F
authors.lastname: Caligaris-Cappio
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D060833:Cellular Microenvironment / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods; D020022:Genetic Predisposition to Disease; D006405:Hematology / Q000379:methods / Q000592:standards / Q000639:trends*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008218:Lymphocytosis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D008954:Models, Biological; D011230:Precancerous Conditions / Q000473:pathology