The CLEC12A receptor marks human basophils

Potential implications for minimal residual disease detection in acute myeloid leukemia

Marie Toft-Petersen, Anne Stidsholt Roug, Trine Plesner, Lene Ebbesen, Gordon D. Brown, Line Nederby

Research output: Contribution to journalArticle

4 Citations (Scopus)
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Abstract

Background: The transmembrane receptor C-type lectin domain family 12, member A (CLEC12A) is known to be highly expressed on monocytes and neutrophils and is a reliable leukemia associated marker in acute myeloid leukemia. Consequently, detailed knowledge of the various normal cell types expressing this receptor is essential. We have observed CLEC12A to be expressed on CD45lowSSClowCD14-CD123+ basophils in peripheral blood (PB) and in the present study, we aimed at verifying this observation and further delineate the CD45lowSSClowCD14-CD123+CLEC12A+ subpopulation.

Methods: We analyzed PB from 20 diagnostic chronic myeloid leukemia (CML) samples and 8 healthy donors in a 6 color multicolor flowcytometry (FCM) based assay. Furthermore, we performed fluorescence activated cell sorting on one CML sample to morphologically confirm the CD45lowSSClowCD14-CD123+CLEC12A+ subset to be highly enriched for basophils. Finally, to further delineate the CD45lowSSClowCD14-CD123+CLEC12A+ subpopulation in normal PB, we examined 3 healthy donors in a 10-color FCM assay enabling further separation of the cell subset into basophils and dendritic cells.

Results: The CLEC12A receptor is expressed on basophils.

Conclusions: Identification and enumeration of basophils is of high relevance in diagnostic hematology and immunology. We here show that CLEC12A in a simple FCM assay consistently marks basophils. Importantly, since basophils are characterized by a CD45lowSSClow profile similar to the “blast-gate” employed for the evaluation of hematological disorders, awareness of minor normal CLEC12A+ subpopulations is crucial when using CLEC12A as a minimal residual disease marker in myeloid malignancies.
Original languageEnglish
Pages (from-to)520-526
Number of pages7
JournalCytometry Part B: Clinical Cytometry
Volume94
Issue number3
Early online date11 Aug 2017
DOIs
Publication statusPublished - May 2018

Fingerprint

C-Type Lectins
Basophils
Residual Neoplasm
Acute Myeloid Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Color
Cell Separation
Hematology
Allergy and Immunology
Dendritic Cells
Monocytes
Flow Cytometry
Leukemia
Neutrophils

Keywords

  • CLEC12A
  • CD371
  • hMICL
  • basophils
  • immunophenotyping

Cite this

The CLEC12A receptor marks human basophils : Potential implications for minimal residual disease detection in acute myeloid leukemia. / Toft-Petersen, Marie; Stidsholt Roug, Anne; Plesner, Trine; Ebbesen, Lene; Brown, Gordon D.; Nederby, Line.

In: Cytometry Part B: Clinical Cytometry, Vol. 94, No. 3, 05.2018, p. 520-526.

Research output: Contribution to journalArticle

Toft-Petersen, Marie ; Stidsholt Roug, Anne ; Plesner, Trine ; Ebbesen, Lene ; Brown, Gordon D. ; Nederby, Line. / The CLEC12A receptor marks human basophils : Potential implications for minimal residual disease detection in acute myeloid leukemia. In: Cytometry Part B: Clinical Cytometry. 2018 ; Vol. 94, No. 3. pp. 520-526.
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abstract = "Background: The transmembrane receptor C-type lectin domain family 12, member A (CLEC12A) is known to be highly expressed on monocytes and neutrophils and is a reliable leukemia associated marker in acute myeloid leukemia. Consequently, detailed knowledge of the various normal cell types expressing this receptor is essential. We have observed CLEC12A to be expressed on CD45lowSSClowCD14-CD123+ basophils in peripheral blood (PB) and in the present study, we aimed at verifying this observation and further delineate the CD45lowSSClowCD14-CD123+CLEC12A+ subpopulation.Methods: We analyzed PB from 20 diagnostic chronic myeloid leukemia (CML) samples and 8 healthy donors in a 6 color multicolor flowcytometry (FCM) based assay. Furthermore, we performed fluorescence activated cell sorting on one CML sample to morphologically confirm the CD45lowSSClowCD14-CD123+CLEC12A+ subset to be highly enriched for basophils. Finally, to further delineate the CD45lowSSClowCD14-CD123+CLEC12A+ subpopulation in normal PB, we examined 3 healthy donors in a 10-color FCM assay enabling further separation of the cell subset into basophils and dendritic cells.Results: The CLEC12A receptor is expressed on basophils.Conclusions: Identification and enumeration of basophils is of high relevance in diagnostic hematology and immunology. We here show that CLEC12A in a simple FCM assay consistently marks basophils. Importantly, since basophils are characterized by a CD45lowSSClow profile similar to the “blast-gate” employed for the evaluation of hematological disorders, awareness of minor normal CLEC12A+ subpopulations is crucial when using CLEC12A as a minimal residual disease marker in myeloid malignancies.",
keywords = "CLEC12A, CD371, hMICL, basophils, immunophenotyping",
author = "Marie Toft-Petersen and {Stidsholt Roug}, Anne and Trine Plesner and Lene Ebbesen and Brown, {Gordon D.} and Line Nederby",
note = "The authors gratefully acknowledge Professor Peter Hokland, Department of Hematology, Aarhus University Hospital for continuous support. This study was financially supported by the Danish Cancer Society. All authors declare no relevant conflicts of interest. Funded by Danish Cancer Society. Grant Number: R90-A6080",
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T1 - The CLEC12A receptor marks human basophils

T2 - Potential implications for minimal residual disease detection in acute myeloid leukemia

AU - Toft-Petersen, Marie

AU - Stidsholt Roug, Anne

AU - Plesner, Trine

AU - Ebbesen, Lene

AU - Brown, Gordon D.

AU - Nederby, Line

N1 - The authors gratefully acknowledge Professor Peter Hokland, Department of Hematology, Aarhus University Hospital for continuous support. This study was financially supported by the Danish Cancer Society. All authors declare no relevant conflicts of interest. Funded by Danish Cancer Society. Grant Number: R90-A6080

PY - 2018/5

Y1 - 2018/5

N2 - Background: The transmembrane receptor C-type lectin domain family 12, member A (CLEC12A) is known to be highly expressed on monocytes and neutrophils and is a reliable leukemia associated marker in acute myeloid leukemia. Consequently, detailed knowledge of the various normal cell types expressing this receptor is essential. We have observed CLEC12A to be expressed on CD45lowSSClowCD14-CD123+ basophils in peripheral blood (PB) and in the present study, we aimed at verifying this observation and further delineate the CD45lowSSClowCD14-CD123+CLEC12A+ subpopulation.Methods: We analyzed PB from 20 diagnostic chronic myeloid leukemia (CML) samples and 8 healthy donors in a 6 color multicolor flowcytometry (FCM) based assay. Furthermore, we performed fluorescence activated cell sorting on one CML sample to morphologically confirm the CD45lowSSClowCD14-CD123+CLEC12A+ subset to be highly enriched for basophils. Finally, to further delineate the CD45lowSSClowCD14-CD123+CLEC12A+ subpopulation in normal PB, we examined 3 healthy donors in a 10-color FCM assay enabling further separation of the cell subset into basophils and dendritic cells.Results: The CLEC12A receptor is expressed on basophils.Conclusions: Identification and enumeration of basophils is of high relevance in diagnostic hematology and immunology. We here show that CLEC12A in a simple FCM assay consistently marks basophils. Importantly, since basophils are characterized by a CD45lowSSClow profile similar to the “blast-gate” employed for the evaluation of hematological disorders, awareness of minor normal CLEC12A+ subpopulations is crucial when using CLEC12A as a minimal residual disease marker in myeloid malignancies.

AB - Background: The transmembrane receptor C-type lectin domain family 12, member A (CLEC12A) is known to be highly expressed on monocytes and neutrophils and is a reliable leukemia associated marker in acute myeloid leukemia. Consequently, detailed knowledge of the various normal cell types expressing this receptor is essential. We have observed CLEC12A to be expressed on CD45lowSSClowCD14-CD123+ basophils in peripheral blood (PB) and in the present study, we aimed at verifying this observation and further delineate the CD45lowSSClowCD14-CD123+CLEC12A+ subpopulation.Methods: We analyzed PB from 20 diagnostic chronic myeloid leukemia (CML) samples and 8 healthy donors in a 6 color multicolor flowcytometry (FCM) based assay. Furthermore, we performed fluorescence activated cell sorting on one CML sample to morphologically confirm the CD45lowSSClowCD14-CD123+CLEC12A+ subset to be highly enriched for basophils. Finally, to further delineate the CD45lowSSClowCD14-CD123+CLEC12A+ subpopulation in normal PB, we examined 3 healthy donors in a 10-color FCM assay enabling further separation of the cell subset into basophils and dendritic cells.Results: The CLEC12A receptor is expressed on basophils.Conclusions: Identification and enumeration of basophils is of high relevance in diagnostic hematology and immunology. We here show that CLEC12A in a simple FCM assay consistently marks basophils. Importantly, since basophils are characterized by a CD45lowSSClow profile similar to the “blast-gate” employed for the evaluation of hematological disorders, awareness of minor normal CLEC12A+ subpopulations is crucial when using CLEC12A as a minimal residual disease marker in myeloid malignancies.

KW - CLEC12A

KW - CD371

KW - hMICL

KW - basophils

KW - immunophenotyping

U2 - 10.1002/cyto.b.21540

DO - 10.1002/cyto.b.21540

M3 - Article

VL - 94

SP - 520

EP - 526

JO - Cytometry Part B: Clinical Cytometry

JF - Cytometry Part B: Clinical Cytometry

SN - 1552-4949

IS - 3

ER -