Monoclonal B cell lymphocytosis: Clinical and population perspectives

Abstract

Monoclonal B Cell Lymphocytosis (MBL) refers to clones of CLL-like cells that exhibit CLL characteris-Five years after the formal description of monoclonal B cell lymphocytosis (MBL) as a uniform nomenclature for CLL-like cells clones that fall short of the numbers required for CLL diagnosis (1,2), the clinical, demographic and molecular features have begun to come into better focus. This report examines offers a clinical perspective on the controversies and suggests studies required for further progress. We discuss the definition, population features, clinical features, molecular components, and finally some recommendations for research directions. DEFINITIONThe original MBL definition (2) consolidated numerous earlier reports of B-cell clones (3,4) noted in diverse settings and distinguished an entity limited to monoclonal B-cell expansions with CLL-like characteristics that did not meet the absolute lymphocyte count (ALC) threshold for CLL. Some related and more rare subgroups (e.g., those with CD20 bright, CD5-cells) were included as distinct subgroups (1,2,5). However, there is an ongoing issue as to whether these should be separated to provide a more CLL-specific MBL definition (6).A recent revision of the definition of CLL has altered the ALC ceiling (7). The revised CLL definition requires an absolute B-lymphocyte count of greater than 5000 cells per cubic milliliter. This has important implications regarding the prevalence of MBL and CLL and the likelihood of a precursor state (MBL) progressing to CLL. Based on this classification change alone, numbers of CLL cases will decrease (because some individuals previously classified as having CLL will now be reclassified as MBL), MBL cases will increase, and the probability of progression to overt CLL will increase.

Case study interpretation—Portland: Case 1

“…In the majority of cases, the monoclonal B‐cells express a CLL‐like immunophenotype (2). The risk of progression varies according to the number of MBL cells and type of MBL (3) with approximately 1% per year risk of progression to CLL requiring treatment (4). The prevalence of MBL reportedly ranges from 3 to 5% (3,000–5,000 in 100,000) in the general population over the age of 50 years (5).…”

HLA specificities are associated with prognosis in IGHV-mutated CLL-like high-count monoclonal B cell lymphocytosis

“…Two groups of CLL-like MBL patients can be differentiated. A small fraction of MBL cases (~10%) are described as high-count MBL (hiMBL), being diagnosed during the characterization of otherwise asymptomatic lymphocytosis with a whole lymphocyte count over 3.5x10 9 /L [ 4 , 5 ]. It is assumed to be a precursor state of CLL, with a progression rate to CLL that requires treatment of ~1–2% per year [ 3 – 7 ].…”

Alterations in the mir-15a/16-1 Loci Impairs Its Processing and Augments B-1 Expansion in De Novo Mouse Model of Chronic Lymphocytic Leukemia (CLL)

“…B-1 cells normally constitute only 5% of total B cells with the major fraction of these cells residing in the peritoneal cavity and a smaller fraction in the spleen. Recent evidence suggests that almost all cases of CLL are preceded by an asymptomatic precursor stage of monoclonal or pauci-clonal B cell lymphocytosis (<5x10 9 /l) termed MBL [ 4 , 5 ]. We have recently shown that NZB mice also exhibit this precursor MBL stage, further validating it as a true model for human CLL [ 6 ].…”