hMICL and CD123 in combination with a CD45/CD34/CD117 backbone – a universal marker combination for the detection of minimal residual disease in acute myeloid leukaemia
Article first published online: 24 OCT 2013
© 2013 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.
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British Journal of Haematology
Volume 164, Issue 2, pages 212–222, January 2014
How to Cite
Roug, A. S., Larsen, H. Ø., Nederby, L., Just, T., Brown, G., Nyvold, C. G., Ommen, H. B. and Hokland, P. (2014), hMICL and CD123 in combination with a CD45/CD34/CD117 backbone – a universal marker combination for the detection of minimal residual disease in acute myeloid leukaemia. British Journal of Haematology, 164: 212–222. doi: 10.1111/bjh.12614
- Issue published online: 3 JAN 2014
- Article first published online: 24 OCT 2013
- Manuscript Accepted: 6 SEP 2013
- Manuscript Received: 20 JUN 2013
- The Danish Cancer Society
- The Danish MRC
- The John and Birthe Meyer Foundation
- Karen Elise Jensen Foundation
- The Wellcome Trust
- acute myeloid leukaemia;
- flow cytometry;
- minimal residual disease;
- quantitative polymerase chain reaction;
- leukaemia-associated immunophenotype
Real-time quantitative polymerase chain reaction (qPCR) has been extensively validated for the detection of minimal residual disease (MRD) in acute myeloid leukaemia (AML). Meanwhile, multicolour flow cytometry (MFC) has received less attention because the so-called leukaemia-associated immunophenotypes (LAIPs) are generally of lower sensitivity and specificity, and prone to change during therapy. To improve MRD assessment by MFC, we here evaluate the combination of human Myeloid Inhibitory C-type Lectin (hMICL, also termed C-type lectin domain family 12, member A, CLEC12A) and CD 123 (also termed interleukin-3 receptor alpha, IL3RA) in combination with CD34 and CD117 (KIT), as an MRD assay in pre-clinical and clinical testing in 69 AML patients. Spiking experiments revealed that the assay could detect MRD down to 10−4 in normal bone marrow with sensitivities equalling those of validated qPCR assays. Moreover, it provided at least one MFC MRD marker in 62/69 patients (90%). High levels of hMICL/CD123 LAIPs at the post-induction time-point were a strong prognostic marker for relapse in patients in haematological complete remission (P < 0·001). Finally, in post induction samples, hMICL/CD123 LAIPs were strongly correlated (r = 0·676, P = 0·0008) to applied qPCR targets. We conclude the hMICL/CD123-based MFC assay is a promising MRD tool in AML.