TY - JOUR
T1 - Applicability and reproducibility of acute myeloid leukaemia stem cell assessment in a multi-centre setting
AU - Hanekamp, Diana
AU - Snel, Alexander N.
AU - Kelder, Angèle
AU - Scholten, Willemijn J.
AU - Khan, Naeem
AU - Metzner, Marlen
AU - Irno-Consalvo, Maria
AU - Sugita, Mayumi
AU - de Jong, Anja
AU - Oude Alink, Sjoerd
AU - Eidhof, Harrie
AU - Wilhelm, Miriam
AU - Feuring-Buske, Michaela
AU - Slomp, Jennichjen
AU - van der Velden, Vincent H.J.
AU - Sonneveld, Edwin
AU - Guzman, Monica
AU - Roboz, Gail J.
AU - Buccisano, Francesco
AU - Vyas, Paresh
AU - Freeman, Sylvie
AU - Bachas, Costa
AU - Ossenkoppele, Gert J.
AU - Schuurhuis, Gerrit J.
AU - Cloos, Jacqueline
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection. Here we present the validation experiments of the assay in several large AML research centres, both in Europe and the United States. Variability within instruments and sample processing showed high correlations between different instruments (Rpearson > 0·91, P < 0·001). Multi-centre testing introduced variation in reported LSC percentages but was found to be below the clinical relevant threshold. Clear gating protocols resulted in all laboratories being able to perform LSC assessment of the validation set. Participating centres were nearly unanimously able to distinguish LSChigh (>0·03% LSC) from LSClow (<0·03% LSC) despite inter-laboratory variation in reported LSC percentages. This study proves that the LSC assay is highly reproducible. These results together with the high prognostic impact of LSC load at diagnosis in AML patients render the one-tube LSC assessment a good marker for future risk classification.
AB - Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection. Here we present the validation experiments of the assay in several large AML research centres, both in Europe and the United States. Variability within instruments and sample processing showed high correlations between different instruments (Rpearson > 0·91, P < 0·001). Multi-centre testing introduced variation in reported LSC percentages but was found to be below the clinical relevant threshold. Clear gating protocols resulted in all laboratories being able to perform LSC assessment of the validation set. Participating centres were nearly unanimously able to distinguish LSChigh (>0·03% LSC) from LSClow (<0·03% LSC) despite inter-laboratory variation in reported LSC percentages. This study proves that the LSC assay is highly reproducible. These results together with the high prognostic impact of LSC load at diagnosis in AML patients render the one-tube LSC assessment a good marker for future risk classification.
UR - http://www.scopus.com/inward/record.url?scp=85082766981&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/bjh.16594
DO - https://doi.org/10.1111/bjh.16594
M3 - Article
C2 - 32239670
SN - 0007-1048
VL - 190
SP - 891
EP - 900
JO - British journal of haematology
JF - British journal of haematology
IS - 6
ER -