Lack of expression of the chondroitin sulphate proteoglycan neuron-glial antigen 2 on candidate stem cell populations in paediatric acute myeloid leukaemia/abn(11q23) and acute lymphoblastic leukaemia/t(4;11).
It has increasingly been acknowledged that only a few leukaemic cells possess the capability to renew themselves and that only these self-renewing leukaemic stem cells are able to initiate relapses. Therefore, these leukaemic stem cells should be the target cells for therapy and for minimal residual disease (MRD) detection. Because of its presence on blasts of 11q23-rearranged high-risk leukaemic patients, neuron-glial antigen 2 (NG2) is thought to be a valuable marker for detecting leukaemic stem cells. Six acute myeloid leukaemia (AML)/abn(11q23) and three acute lymphoblastic leukaemia (ALL)/t(4;11) samples were analysed by four-colour flow cytometry for NG2 expression on primitive cell populations. Candidate leukaemic cell populations were defined by the antigen profiles CD34+CD38- in AML and CD34+CD19-CD117+ in ALL. Surprisingly, in all patients these candidate stem cell populations were shown to lack expression of NG2. Instead, a correlation between the expression of the myeloid differentiation marker CD33 and increasing levels of NG2 on maturing cells could be demonstrated. Similarly, in ALL patients CD34+CD19+ cells showed a higher expression of NG2 mRNA compared with CD34+CD19-. Thus, NG2 appears to be upregulated with differentiation and not to be expressed on primitive disease-maintaining cells. This hampers the clinical use of NG2 as a therapeutic target and as a sensitive marker for MRD detection.
Neudenberger
J
J
Department of Paediatric Haematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.
Hotfilder
M
M
Rosemann
A
A
Langebrake
C
C
Reinhardt
D
D
Pieters
R
R
Schrauder
A
A
Schrappe
M
M
Röttgers
S
S
Harbott
J
J
Vormoor
J
J
D000208:Acute Disease; D000941:Antigens / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D063268:Sialic Acid Binding Ig-like Lectin 3; D014178:Translocation, Genetic; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011509:Proteoglycans; D063268:Sialic Acid Binding Ig-like Lectin 3; D000099216:Chondroitin Sulfate Proteoglycan 4; C571163:CD33 protein, human