Characterization of CD34<sup>+</sup> hematopoietic cells in systemic mastocytosis: Potential role in disease dissemination

Mayado, Andrea; Teodósio, Cristina; Dasilva-Freire, Noelia; Jara‐Acevedo, María; García‐Montero, Andrés C.; Álvarez‐Twose, Iván; Sánchez‐Muñoz, Laura; Matito, Almudena; Caldas, Carolina; Muñoz‐González, Javier I.; Henriques, Ana; Sánchez-Gallego, José I.; Escribano, Luís; Órfão, Alberto

doi:10.1111/all.13413

Cited by 13 publications

(16 citation statements)

References 48 publications

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“…Previous studies have shown that eosinophils are usually clonal in patients with advanced SM [17][18][19]. However, eosinophilia can also be caused by other pathologic conditions such as parasitosis, drug reactions, or atopia.…”

Section: Discussionmentioning

confidence: 99%

“…Note that for PFS, the Y-axis is cut at 40%. The p value refers to the comparison of the survival curves as assessed by log rank test 230 1711 (21) 15 (19) 3 1028 (14) 705 (30) Organomegaly, number (%) 1 72 721 (8) 21 7108 (8) 35 ( 12 467 54 814 183 (10) 37 (18) 159 (7) Number absolute eosinophils > 1.5 × 10 9 /l (% of that category) 0 0 0 0 10 13 611 (14) 5 (17) 45 (22) 74 (…”

Section: Supplementary Materialsmentioning

confidence: 99%

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Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry

et al. 2019

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Author contributions HCK-N had the conceptual idea, helped with the analyses, and wrote the paper. WRS did all analyses, was responsible for data collection and correction in the ECNM database, designed all figures, and cowrote the article. AI and KH did the initial analyses and corrected the final version of the manuscript. BvA and LRFS were helpful in discussions and helped with entry of patient data and corrected the final version of the manuscript.

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Section: Discussionmentioning

confidence: 99%

Section: Supplementary Materialsmentioning

confidence: 99%

Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry

et al. 2019

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“…64 Cell culture experiments of CD34 1 CD203c 1 bone marrow progenitors show evidence of mast cell-forming potential and considerable basophil-forming potential; however, the mast cell-forming potential is comparable in the CD34 1 CD203c 2 and CD34 1 CD203c 1 fractions. 64 Still, recent data suggest that CD203c in combination with other markers enrich for mast cell progenitors, 65 likely the more differentiated ones, although this needs to be verified experimentally.…”

Section: Identification Of Early Progenitors With Mast Cell-forming Cmentioning

confidence: 99%

“…56,67 An independent study showed that these progenitors fully agree in phenotype and frequency with the CD34 1 c-Kit hi HLA-DR 2/int CD203c 1 gating strategy used for identifying a putative peripheral blood mast cell progenitor. 65 The Lin 2 CD34 1 c-Kit int/hi FceRI 1 cells constitute unipotent (or almost committed) progenitors, which are further characterized by the expression of CD123 and integrin b7 and absence of CD45RA and CRTH2, placing the cells in the classic CMP sorting gate. 56,67 However, this does not necessarily mean that mast cells are derived from CMPs.…”

Section: Identification Of Early Progenitors With Mast Cell-forming Cmentioning

confidence: 99%

Deciphering the differentiation trajectory from hematopoietic stem cells to mast cells

Grootens¹,

Ungerstedt²,

Nilsson³

et al. 2018

Blood Advances

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Hematopoietic stem cells differentiate into all types of blood cells, including peripheral tissue-resident mast cells. The early mast cell differentiation takes place in the bone marrow, after which the progenitor cells enter the circulation and mature once reaching their target organ. Early results from single-cell culture experiments and colony-forming assays have produced the classic hierarchical tree model of hematopoiesis. The introduction of high-throughput, single-cell RNA sequencing is now revolutionizing our understanding of the differentiation process, questioning the classic tree-based models. By integrating the results from early cell culture experiments with single-cell transcriptomics, we present a differentiation landscape model of hematopoiesis and discuss it with focus on mast cells. The review also describes how the hematologic neoplasm systemic mastocytosis can be used to model human hematopoiesis using naturally occurring cell barcoding by means of the common D816V mutation.

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“…11 When the KIT D816V mutation is present in mast cells, it may also be detected in mature bone marrow or peripheral blood cells, such as basophils, eosinophils, neutrophils, and B and T lymphocytes, which depends on the patient. 12–17 Furthermore, the precursors of erythroid and myeloid cells as well as CD34 + progenitors may carry the KIT D816V mutation. 12,18,19 Taken together, these findings suggest that the mutation may arise in early hematopoietic stem and progenitor cells (HSPCs), rather than in a lineage-restricted precursor.…”

Section: Introductionmentioning

confidence: 99%

Single-cell analysis reveals the KIT D816V mutation in hematopoietic stem and progenitor cells in systemic mastocytosis: Supplementary data

Grootens

Ungerstedt

Ekoff

et al. 2018

Preprint

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32Background: Systemic mastocytosis (SM) is a hematological disease characterized 33 by organ infiltration by neoplastic mast cells. Almost all SM patients have a mutation 34 in the gene encoding the tyrosine kinase receptor KIT causing a D816V substitution 35 and autoactivation of the receptor. Mast cells and CD34 + hematopoietic progenitors 36 can carry the mutation, however, in which progenitor cell subset the mutation arises is 37 unknown. We aimed to investigate the distribution of the D816V mutation in single 38 mast cells and single hematopoietic stem and progenitor cells. 39Methods: Fluorescence-activated single-cell index sorting and D816V mutation 40 assessment were applied to analyze mast cells and more than 10,000 CD34 + bone 41 marrow progenitors across 10 hematopoietic progenitor subsets. In vitro assays 42 verified cell-forming potential. 43Findings: We found that in SM 60-99% of the mast cells harbored the D816V 44 mutation. Despite increased frequencies of mast cells in SM patients compared with 45 control subjects, the hematopoietic progenitor subset frequencies were comparable. 46Nevertheless, the mutation could be detected throughout the hematopoietic landscape 47 of SM patients, from hematopoietic stem cells to more lineage-primed progenitors. In 48 addition, we demonstrate that FcεRI + bone marrow progenitors exhibit mast cell-49 forming potential, and we describe aberrant CD45RA expression on SM mast cells for 50 the first time. 51Interpretation: The KIT D816V mutation arises in early hematopoietic stem and 52 progenitor cells and the mutation frequency is approaching 100% in mature mast 53 cells, which express the aberrant marker CD45RA. 54 55

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Characterization of CD34⁺ hematopoietic cells in systemic mastocytosis: Potential role in disease dissemination

Abstract: The presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34 HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34 HPC potentially contributing to early dissemination of the disease.

Cited by 13 publications

References 48 publications

Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry

Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry

Deciphering the differentiation trajectory from hematopoietic stem cells to mast cells

Single-cell analysis reveals the KIT D816V mutation in hematopoietic stem and progenitor cells in systemic mastocytosis: Supplementary data

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Characterization of CD34+ hematopoietic cells in systemic mastocytosis: Potential role in disease dissemination

Abstract: The presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34 HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34 HPC potentially contributing to early dissemination of the disease.

Cited by 13 publications

References 48 publications

Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry

Prognostic impact of eosinophils in mastocytosis: analysis of 2350 patients collected in the ECNM Registry

Deciphering the differentiation trajectory from hematopoietic stem cells to mast cells

Single-cell analysis reveals the KIT D816V mutation in hematopoietic stem and progenitor cells in systemic mastocytosis: Supplementary data

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Characterization of CD34⁺ hematopoietic cells in systemic mastocytosis: Potential role in disease dissemination