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

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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 languageEnglish
Pages (from-to)393-401
Number of pages9
JournalBritish Journal of Haematology
Volume175
Issue number3
Early online date9 Sep 2016
DOIs
Publication statusPublished - Nov 2016

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C-Type Lectins
Neoplastic Stem Cells
Myelodysplastic Syndromes
Stem Cells
Acute Myeloid Leukemia
Immunophenotyping
Residual Neoplasm
Hematopoietic Stem Cells
Leukemia

Keywords

  • cancer stem cells
  • myelodysplastic syndrome
  • hMICL
  • CD371
  • LTC-IC

Cite this

Toft-Petersen, M., Nederby, L., Kjeldsen, E., Kerndrup, G. B., Brown, G. D., Hokland, P., & Stidsholt Roug, A. (2016). Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome. British Journal of Haematology, 175(3), 393-401. https://doi.org/10.1111/bjh.14270

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome. / Toft-Petersen, Marie; Nederby, Line; Kjeldsen, Eigil; Kerndrup, Gitte B; Brown, Gordon D; Hokland, Peter; Stidsholt Roug, Anne.

In: British Journal of Haematology, Vol. 175, No. 3, 11.2016, p. 393-401.

Research output: Contribution to journalArticle

Toft-Petersen, M, Nederby, L, Kjeldsen, E, Kerndrup, GB, Brown, GD, Hokland, P & Stidsholt Roug, A 2016, 'Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome', British Journal of Haematology, vol. 175, no. 3, pp. 393-401. https://doi.org/10.1111/bjh.14270
Toft-Petersen M, Nederby L, Kjeldsen E, Kerndrup GB, Brown GD, Hokland P et al. Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome. British Journal of Haematology. 2016 Nov;175(3):393-401. https://doi.org/10.1111/bjh.14270
Toft-Petersen, Marie ; Nederby, Line ; Kjeldsen, Eigil ; Kerndrup, Gitte B ; Brown, Gordon D ; Hokland, Peter ; Stidsholt Roug, Anne. / Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome. In: British Journal of Haematology. 2016 ; Vol. 175, No. 3. pp. 393-401.
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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.",
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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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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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