Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia

Selimoglu-Buet, Dorothée; Wagner-Ballon, Orianne; Saada, Véronique; Bardet, Valérie; Itzykson, Raphaël; Bencheikh, Laura; Morabito, Margot; Met, Elisabeth; Debord, Camille; Benayoun, Emmanuel; Nloga, Anne Marie; Fenaux, Pierre; Braun, Thorsten; Willekens, Christophe; Quesnel, Bruno; Adès, Lionel; Fontenay, Michaëla; Rameau, Philippe; Droin, Nathalie; Koscielny, Serge; Solary, Éric

doi:10.1182/blood-2015-01-620781

Cited by 221 publications

(258 citation statements)

References 52 publications

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“…[55][56][57][58][59] Pathologically, a recent study by Solary et al demonstrated that the characteristic monocytosis is, in fact, an expansion of classical monocytes with reduction of other nonclassical monocytic subtypes. 60 This phenotype was present across all patients studied and was capable of distinguishing CMML from other entities with benign causes of monocytosis. 60 Classical monocytes represent the inflammatory monocytic subset and are preferentially recruited to sites of tissue injury or infection via the CCR2-CCL2 axis, which is upregulated in CMML.…”

Section: Inflammatory and Cell Extrinsic Phenotypesmentioning

confidence: 81%

“…60 This phenotype was present across all patients studied and was capable of distinguishing CMML from other entities with benign causes of monocytosis. 60 Classical monocytes represent the inflammatory monocytic subset and are preferentially recruited to sites of tissue injury or infection via the CCR2-CCL2 axis, which is upregulated in CMML. The association between classical monocytosis and CMML is so robust that this assay is now being validated as a diagnostic modality in CMML.…”

Section: Inflammatory and Cell Extrinsic Phenotypesmentioning

confidence: 81%

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When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the genomic box in chronic myelomonocytic leukemia

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2016

Blood

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Exome sequencing studies in chronic myelomonocytic leukemia (CMML) illustrate a mutational landscape characterized by few somatic mutations involving a subset of recurrent gene mutations in ASXL1, SRSF2, and TET2, each approaching 40% in incidence. This has led to the clinical implementation of next-generation sequencing panels that effectively identify clonal monocytosis and complement clinical prognostic scoring systems in most patients. However, most murine models based on single gene mutations fail to recapitulate the CMML phenotype, and many gene mutations are loss of function, making the identification of traditional therapeutic vulnerabilities challenging. Further, as a subtype of the myelodysplastic/myeloproliferative neoplasms, CMML has a complex clinical heterogeneity not reflected by the mutational landscape. In this review, we will discuss the discordance between mutational homogeneity and clinical complexity and highlight novel genomic and nongenomic approaches that offer insight into the underlying clinical characteristics of CMML.

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Section: Inflammatory and Cell Extrinsic Phenotypesmentioning

confidence: 81%

Section: Inflammatory and Cell Extrinsic Phenotypesmentioning

confidence: 81%

When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the genomic box in chronic myelomonocytic leukemia

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2016

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“…Researchers compared the population of monocytes among healthy bone marrow donors, patients with reactive monocytosis, another hematologic malignancy, and CMML patients, which demonstrate a characteristic increase in the fraction of CD14+/CD16− cells compared with the other samples [23].…”

Section: Classical Monocytes Cd14mentioning

confidence: 99%

Phenotypic Markers and Functional Regulators of Myelomonocytic Cells

Marti¹,

Bacal²,

CamerãoBento³

et al. 2017

Biology of Myelomonocytic Cells

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In this chapter, there is a description of hematopoietic stem cells, maturation curve and their differentiation into myeloid cells, including phenotypes and transcription factors involved in this process. Further, we discuss myeloid maturation curve from myeloid precursor, monoblast, premonocyte to monocytes, and also monocytes subsets regarding their CD14 and CD16 expressions and related functions in health and disease. In addition, we reason about the differentiation from monocytes either in dendritic cells or in macrophages in vitro using differential growth factors; these cells are differentiated from those found in vivo being named as monocyte-derived cells. Furthermore, we explore distinguished phenotype of monocytes, macrophages, and dendritic cells monocyte-derived in vitro, using confocal microscopy and flow cytometry, in order to display morphological and phenotypic differences among them.

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“…Reactive monocytoses, e.g., caused by chronic infections or inflammation, are associated with expansion of intermediate (CD14+/CD16+) and non-classical (CD14−/CD16+) monocytes, whereas a proportion of 'classical' CD14+/ Monocytosis persistent for at least 3 months, with other causes excluded CD16− monocytes >94% predicts CMML with good accuracy ( Fig. 1) [25].…”

Section: Diagnostic Criteriamentioning

confidence: 99%

“…Recurrent oncogenes can be broadly stratified into four distinct families, with a certain degree of mutual exclusion [25] within each of these families (Fig. 2).…”

Section: Molecular Lesions and Pathogenesismentioning

confidence: 99%

CMML: Clinical and molecular aspects

et al. 2017

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Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia

Abstract: Key Points An increase in the classical monocyte subset to >94% of total monocytes discriminates CMML from other monocytoses with high specificity. This characteristic increase in classical monocytes disappears in CMML patients who respond to hypomethylating agents.

Cited by 221 publications

References 52 publications

When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the genomic box in chronic myelomonocytic leukemia

When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the genomic box in chronic myelomonocytic leukemia

Phenotypic Markers and Functional Regulators of Myelomonocytic Cells

CMML: Clinical and molecular aspects

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