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h MICL and CD 123 in combination with a CD 45/ CD 34/ CD 117 backbone – a universal marker combination for the detection of minimal residual disease in acute myeloid leukaemia
Author(s) -
Roug Anne S.,
Larsen Hanne Ø.,
Nederby Line,
Just Tom,
Brown Gordon,
Nyvold Charlotte G.,
Ommen Hans B.,
Hokland Peter
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12614
Subject(s) - minimal residual disease , flow cytometry , cd117 , cytometry , microbiology and biotechnology , real time polymerase chain reaction , myeloid , cd34 , cfu gm , chemistry , immunology , medicine , bone marrow , biology , haematopoiesis , stem cell , biochemistry , genetics , gene
Summary Real‐time quantitative polymerase chain reaction (q PCR ) 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 ( LAIP s) 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 L ectin (h MICL , also termed C ‐type lectin domain family 12, member A , CLEC 12 A ) 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 q PCR assays. Moreover, it provided at least one MFC MRD marker in 62/69 patients (90%). High levels of h MICL / CD 123 LAIP s 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, h MICL / CD 123 LAIPs were strongly correlated ( r = 0·676, P = 0·0008) to applied q PCR targets. We conclude the h MICL / CD 123‐based MFC assay is a promising MRD tool in AML .