Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome.
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.
Department of Haematology, Aarhus University Hospital, Aarhus, Denmark. marie.toft-petersen@clin.au.dk.
Marie
M
Toft-Petersen
Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
Line
L
Nederby
Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
Eigil
E
Kjeldsen
Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Gitte B
GB
Kerndrup
Immunity, Infection and Inflammation Programme, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Gordon D
GD
Brown
Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
Peter
P
Hokland
Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.
Anne
A
Stidsholt Roug
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D014408:Biomarkers, Tumor; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D014408:Biomarkers, Tumor; C485220:CLEC12A protein, human; D037181:Lectins, C-Type; D011975:Receptors, Mitogen

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