Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

Marie Toft-Petersen; Line Nederby; Eigil Kjeldsen; Gitte B Kerndrup; Gordon D Brown; Peter Hokland; Anne Stidsholt Roug

doi:10.1111/bjh.14270

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

Marie Toft-Petersen, Line Nederby, Eigil Kjeldsen, Gitte B Kerndrup, Gordon D Brown, Peter Hokland, Anne Stidsholt Roug

Applied Medicine

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Abstract

Evidence of distinct disease propagating stem cells in myelodysplastic syndrome (MDS) has emerged in recent years. However, immunophenotypic characterization of these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have previously described aberrant expression of the C-type lectin domain family 12, member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a tool for assessing minimal residual disease. Furthermore, CLEC12A has been proposed as a promising marker of leukaemic stem cells in AML. The role of CLEC12A in MDS, however, remains to be elucidated. In this study, we found CLEC12A aberrantly expressed on the CD34(+) CD38(-) cell compartment in 71% (22/31) of MDS patients, distributed across all Revised International Prognostic Scoring System risk groups. We showed that the CD34(+) CD38(-) CLEC12A(+) cells were indeed malignant and possessed functional stem cell properties in the long-term colony-initiating cell assay. As opposed to reported findings in AML, we showed that cancer stem cells from MDS samples derived from both CLEC12A positive and negative CD34(+) CD38(-) subpopulations. Due to the absence of CLEC12A on normal haematopoietic stem cells, CLEC12A stem cell immunophenotyping may contribute to diagnosing and monitoring MDS patients and could furthermore add knowledge about disease propagating cells in MDS.

Original language	English
Pages (from-to)	393-401
Number of pages	9
Journal	British Journal of Haematology
Volume	175
Issue number	3
Early online date	9 Sept 2016
DOIs	https://doi.org/10.1111/bjh.14270
Publication status	Published - Nov 2016

Bibliographical note

Acknowledgements
The authors would like to thank Petter S. Woll, MSc, PhD, Karolinska Institutet, Stockholm, Sweden, for the kind and generous supervision of the LTC-IC experiments. We thank the FACS Core Facility at Aarhus University for access to the cell sorter and Pia S. Kristensen, Department of Haematology, Aarhus University Hospital for her excellent technical assistance conducting the FISH experiments. The Karen Elise Jensen Foundation, The Meyer Foundation, The Wellcome Trust and the Danish Cancer Society supported the study.

Keywords

cancer stem cells
myelodysplastic syndrome
hMICL
CD371
LTC-IC

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Unravelling the relevance of CLEC12A as a cancer stem cellmarker in myelodysplastic syndrome
© 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
Final published version, 383 KBLicence: CC BY

Cite this

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title = "Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome",

abstract = "Evidence of distinct disease propagating stem cells in myelodysplastic syndrome (MDS) has emerged in recent years. However, immunophenotypic characterization of these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have previously described aberrant expression of the C-type lectin domain family 12, member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a tool for assessing minimal residual disease. Furthermore, CLEC12A has been proposed as a promising marker of leukaemic stem cells in AML. The role of CLEC12A in MDS, however, remains to be elucidated. In this study, we found CLEC12A aberrantly expressed on the CD34(+) CD38(-) cell compartment in 71% (22/31) of MDS patients, distributed across all Revised International Prognostic Scoring System risk groups. We showed that the CD34(+) CD38(-) CLEC12A(+) cells were indeed malignant and possessed functional stem cell properties in the long-term colony-initiating cell assay. As opposed to reported findings in AML, we showed that cancer stem cells from MDS samples derived from both CLEC12A positive and negative CD34(+) CD38(-) subpopulations. Due to the absence of CLEC12A on normal haematopoietic stem cells, CLEC12A stem cell immunophenotyping may contribute to diagnosing and monitoring MDS patients and could furthermore add knowledge about disease propagating cells in MDS.",

keywords = "cancer stem cells, myelodysplastic syndrome, hMICL, CD371, LTC-IC",

author = "Marie Toft-Petersen and Line Nederby and Eigil Kjeldsen and Kerndrup, {Gitte B} and Brown, {Gordon D} and Peter Hokland and {Stidsholt Roug}, Anne",

note = "Acknowledgements The authors would like to thank Petter S. Woll, MSc, PhD, Karolinska Institutet, Stockholm, Sweden, for the kind and generous supervision of the LTC-IC experiments. We thank the FACS Core Facility at Aarhus University for access to the cell sorter and Pia S. Kristensen, Department of Haematology, Aarhus University Hospital for her excellent technical assistance conducting the FISH experiments. The Karen Elise Jensen Foundation, The Meyer Foundation, The Wellcome Trust and the Danish Cancer Society supported the study.",

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AU - Brown, Gordon D

AU - Hokland, Peter

AU - Stidsholt Roug, Anne

N1 - Acknowledgements The authors would like to thank Petter S. Woll, MSc, PhD, Karolinska Institutet, Stockholm, Sweden, for the kind and generous supervision of the LTC-IC experiments. We thank the FACS Core Facility at Aarhus University for access to the cell sorter and Pia S. Kristensen, Department of Haematology, Aarhus University Hospital for her excellent technical assistance conducting the FISH experiments. The Karen Elise Jensen Foundation, The Meyer Foundation, The Wellcome Trust and the Danish Cancer Society supported the study.

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N2 - Evidence of distinct disease propagating stem cells in myelodysplastic syndrome (MDS) has emerged in recent years. However, immunophenotypic characterization of these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have previously described aberrant expression of the C-type lectin domain family 12, member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a tool for assessing minimal residual disease. Furthermore, CLEC12A has been proposed as a promising marker of leukaemic stem cells in AML. The role of CLEC12A in MDS, however, remains to be elucidated. In this study, we found CLEC12A aberrantly expressed on the CD34(+) CD38(-) cell compartment in 71% (22/31) of MDS patients, distributed across all Revised International Prognostic Scoring System risk groups. We showed that the CD34(+) CD38(-) CLEC12A(+) cells were indeed malignant and possessed functional stem cell properties in the long-term colony-initiating cell assay. As opposed to reported findings in AML, we showed that cancer stem cells from MDS samples derived from both CLEC12A positive and negative CD34(+) CD38(-) subpopulations. Due to the absence of CLEC12A on normal haematopoietic stem cells, CLEC12A stem cell immunophenotyping may contribute to diagnosing and monitoring MDS patients and could furthermore add knowledge about disease propagating cells in MDS.

AB - Evidence of distinct disease propagating stem cells in myelodysplastic syndrome (MDS) has emerged in recent years. However, immunophenotypic characterization of these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have previously described aberrant expression of the C-type lectin domain family 12, member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a tool for assessing minimal residual disease. Furthermore, CLEC12A has been proposed as a promising marker of leukaemic stem cells in AML. The role of CLEC12A in MDS, however, remains to be elucidated. In this study, we found CLEC12A aberrantly expressed on the CD34(+) CD38(-) cell compartment in 71% (22/31) of MDS patients, distributed across all Revised International Prognostic Scoring System risk groups. We showed that the CD34(+) CD38(-) CLEC12A(+) cells were indeed malignant and possessed functional stem cell properties in the long-term colony-initiating cell assay. As opposed to reported findings in AML, we showed that cancer stem cells from MDS samples derived from both CLEC12A positive and negative CD34(+) CD38(-) subpopulations. Due to the absence of CLEC12A on normal haematopoietic stem cells, CLEC12A stem cell immunophenotyping may contribute to diagnosing and monitoring MDS patients and could furthermore add knowledge about disease propagating cells in MDS.

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KW - myelodysplastic syndrome

KW - hMICL

KW - CD371

KW - LTC-IC

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DO - 10.1111/bjh.14270

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SN - 0007-1048

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SP - 393

EP - 401

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 3

ER -

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

Abstract

Bibliographical note

Keywords

UN SDGs

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