Non‐CLL‐like monoclonal B‐cell lymphocytosis in the general population: Prevalence and phenotypic/genetic characteristics

Nieto, Wendy G.; Teodósio, Cristina; López, Antonio; Rodríguez-Caballero, Arancha; Romero, Alfonso E.; Bárcena, Paloma; Gutiérrez, María Laura; Langerak, Anton W.; Fernández-Navarro, Paulino; Órfão, Alberto; Almeida, Júlia

doi:10.1002/cyto.b.20543

Cited by 43 publications

(40 citation statements)

References 29 publications

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“…In contrast, about 50% of the individuals harboring atypical CLL MBL and MBL CD5 (À) at the time of diagnosis lost this condition within 3 years, indicating that the presence of these cells is transient in nature. These results differed from a previous study (7) in which 12 atypical CLL MBL and MBL CD5 (À) cases were shown to persist 1 year after the initial diagnosis. According to our model, these seemingly different findings are not contradictory.…”

Section: Interpreting Data That Document the Presence Of Cancerassocicontrasting

confidence: 99%

“…To test this notion, cohorts of healthy people that harbor aberrant cells should be followed longitudinally to determine the fate of these cells, i.e., whether their presence is transient or not. This analysis can be performed using the same experimental techniques described in the studies discussed above (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). When testing for the presence of aberrant cells in the blood, the average telomere length should be determined both in the aberrant cells and in the normal cells of these individuals (in blood average, telomere length can be efficiently measured using flow FISH cytometry; ref.…”

Section: Translatable and Testable Insightsmentioning

confidence: 99%

“…All cases of CLL seem to arise from MBL, although the majority of MBL cases do not give rise to proliferative disorders (6). Intriguingly longitudinal studies of both t (14;18) and MBL suggest that these abnormalities persist for long periods of time in some individuals (7)(8)(9)(10) and are transient, completely disappearing in others (9)(10)(11). In this article, we present a cell lineage model based on the concept of fitness in evolutionary theory and cellular replication limits, which provides an explanation for these phenomena.…”

Section: Introductionmentioning

confidence: 99%

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Cancer-Associated Mutations in Healthy Individuals: Assessing the Risk of Carcinogenesis

2014

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Mutations associated with hematopoietic malignancies have been repeatedly identified in healthy individuals. For certain cases, such as the t(14;18) translocation and monoclonal B-cell lymphocytosis, no clear link between the presence of aberrant cells and the later development of cancer has been established. Intriguingly, longitudinal studies suggest that these abnormalities persist for long periods of time in some individuals, but in others are transient in which they disappear completely. Here, we present a mathematical model, based on cellular replication limits, that provides a possible explanation for these seemingly contradictory findings. It proposes that the transient and persistent nature of the phenotypes depends on the stage in the differentiation pathway of a given lineage in which the mutation originates. Our work suggests that cellular replication limits may not only prevent cancer by aborting clonal expansion of cells, but also by influencing the fate of altered but nonneoplastic cells in healthy tissue. Cancer Res; 74(6);

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Section: Interpreting Data That Document the Presence Of Cancerassocicontrasting

confidence: 99%

Section: Translatable and Testable Insightsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cancer-Associated Mutations in Healthy Individuals: Assessing the Risk of Carcinogenesis

2014

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“…Our results differ from those recently published in a series of 12 atypical-CLL and CD5 Ϫ MBL reevaluated 12 months after the first immunophenotypic analysis. 24 All clones were confirmed and even showed a significant increase in the median concentration of clonal B cells. Although this discrepancy may be accounted for both by the original higher median value of the clonal populations and especially by the different length of the follow-up, further studies with larger cohorts are needed to settle the issue.…”

Section: Discussionmentioning

confidence: 89%

General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL

Fazi

Scarfò

Pecciarini

et al. 2011

Blood

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“…Instrument setup, calibration, and daily monitoring were performed according to well-established protocols [23]. MBL classification into CLL-like and non-CLL-like MBL categories were based on consensus criteria [4,24,25]. The following B-cell populations were identified [15,16]: immature B-cells: CD10 1 CD19 1 CD20 1 CD27 -CD38 1 ; naive B-lymphocytes: CD10 -CD19 1 CD20 1 CD27 -CD38 -IgM 1 ; memory B-lymphocytes: CD10 -CD19 1 CD20 1 CD27 1 CD38 -; and plasmablasts: CD10 -CD19 1 CD20 -/ 1d CD27 hi CD38 hi ).…”

Section: Methodsmentioning

confidence: 99%

Monoclonal B‐cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B‐cell subsets

et al. 2012

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Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets. Little is known about the distribution of normal lymphoid cells and their subsets in the peripheral blood (PB) of subjects with monoclonal Bcell lymphocytosis (MBL). In our study, we compared the absolute number of PB lymphoid cells and their subpopulations in 95 MBL cases with normal lymphocyte counts vs. 617 age-/sex-matched non-MBL healthy subjects (controls), using highly sensitive flow cytometry. MBL cases showed significantly reduced numbers of normal circulating B-cells, at the expense of immature and naïve B-cells; in addition, CD41CD81 double-positive T-cells and CD81 T-cells were significantly lower and higher vs. controls, respectively. Moreover, most normal B-cell subsets were significantly decreased in PB at 1% MBL-counts, vs. ''low-count'' MBL cases, and lower amounts of immature/naïve B-cells were detected in biclonal (particularly in cases with coexisting CLL-like-and non-CLL-like B-cell clones) vs. monoclonal MBL subjects. In summary, our results show imbalanced (reduced) absolute numbers of recently produced normal circulating B-cells (e.g., immature and naïve B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.The revised National Cancer Institute Working Group/International Workshop on chronic lymphocytic leukemia (CLL) recognized monoclonal B-cell lymphocytosis (MBL) as a new diagnostic category defined by presence of <5 3 10 9 /L circulating monoclonal B-cells -most frequently resembling the phenotype and genetic features of CLL cells-in otherwise healthy subjects [1][2][3][4]. It has been suggested that the clinical significance of MBL is different depending on whether a given MBL is identified during the diagnostic evaluation of a lymphocytosis or through screening procedures of subjects with normal lymphocyte counts [3]; accordingly, the probability of MBL to progress to CLL increases among cases showing higher B-cell numbers [3,[5][6][7][8][9][10][11][12][13]. Other factors predicting transformation of MBL into CLL have not been clarified [5][6][7][8][9][10][11][12][13]; the evidences of NK-and T-cell alterations in CLL, which have been suggested to contribute to the survival of CLL B-cells and progression of the disease [13,14], prompted us to evaluate the distribution of different compartments of circulating normal lymphoid cells in MBL cases, to gain insight into its potential impact on MBL biology. With this purpose, we analyzed the distribution of non-clonal lymphoid cells (B-, T-, and NK-cells) and their subsets in PB specimens from MBL cases with normal lymphocyte counts, and their relationship with MBL-cell counts.Overall, MBL showed significantly decreased normal B-lymphocytes counts vs. controls, at the expense of lower numbers of both PB immature and naïve B-lymphocytes (Fig. 1A). As the distribution of B-cell subsets markedly varies with age [15,16], further comparison of the number of B-cells and their subp...

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Non‐CLL‐like monoclonal B‐cell lymphocytosis in the general population: Prevalence and phenotypic/genetic characteristics

Cited by 43 publications

References 29 publications

Cancer-Associated Mutations in Healthy Individuals: Assessing the Risk of Carcinogenesis

Cancer-Associated Mutations in Healthy Individuals: Assessing the Risk of Carcinogenesis

General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL

Monoclonal B‐cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B‐cell subsets

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