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

Anne S. Roug, Hanne O. Larsen, Line Nederby, Tom Just, Gordon Brown, Charlotte G. Nyvold, Hans B. Ommen, Peter Hokland* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)212-222
Number of pages11
JournalBritish Journal of Haematology
Volume164
Issue number2
Early online date24 Oct 2013
DOIs
Publication statusPublished - 1 Jan 2014

Fingerprint

Residual Neoplasm
Acute Myeloid Leukemia
Flow Cytometry
C-Type Lectins
Leukemia
Interleukin-3 Receptors
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Bone Marrow
Recurrence
Sensitivity and Specificity

Keywords

  • Acute myeloid leukaemia
  • Flow cytometry
  • Leukaemia-associated immunophenotype
  • Minimal residual disease
  • Quantitative polymerase chain reaction

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Roug, Anne S.; Larsen, Hanne O.; Nederby, Line; Just, Tom; Brown, Gordon; Nyvold, Charlotte G.; Ommen, Hans B.; Hokland, Peter (Corresponding Author).

In: British Journal of Haematology, Vol. 164, No. 2, 01.01.2014, p. 212-222.

Research output: Contribution to journalArticle

Roug, Anne S. ; Larsen, Hanne O. ; Nederby, Line ; Just, Tom ; Brown, Gordon ; Nyvold, Charlotte G. ; Ommen, Hans B. ; Hokland, Peter. / 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. In: British Journal of Haematology. 2014 ; Vol. 164, No. 2. pp. 212-222.
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abstract = "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.",
keywords = "Acute myeloid leukaemia, Flow cytometry, Leukaemia-associated immunophenotype, Minimal residual disease, Quantitative polymerase chain reaction",
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note = "The work was supported by grants to PH from The Danish Cancer Society, The Danish MRC, The John and Birthe Meyer Foundation, and the Karen Elise Jensen Foundation. GB has received funding from The Wellcome Trust. We thank our patients for contributing samples, and for continuous input during these efforts.",
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AU - Larsen, Hanne O.

AU - Nederby, Line

AU - Just, Tom

AU - Brown, Gordon

AU - Nyvold, Charlotte G.

AU - Ommen, Hans B.

AU - Hokland, Peter

N1 - The work was supported by grants to PH from The Danish Cancer Society, The Danish MRC, The John and Birthe Meyer Foundation, and the Karen Elise Jensen Foundation. GB has received funding from The Wellcome Trust. We thank our patients for contributing samples, and for continuous input during these efforts.

PY - 2014/1/1

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N2 - 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.

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