Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid Leukemia
The assessment of minimal residual disease (MRD) is increasingly considered to monitor response to therapy in hematological malignancies. In acute myeloblastic leukemia (AML), molecular MRD (mMRD) is possible for about half the patients while multiparameter flow cytometry (MFC) is more broadly avail...
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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/2072-6694/13/4/629 |
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| author | Jean Philippe Vial Nicolas Lechevalier Francis Lacombe Pierre-Yves Dumas Audrey Bidet Thibaut Leguay François Vergez Arnaud Pigneux Marie C. Béné |
| author_facet | Jean Philippe Vial Nicolas Lechevalier Francis Lacombe Pierre-Yves Dumas Audrey Bidet Thibaut Leguay François Vergez Arnaud Pigneux Marie C. Béné |
| author_sort | Jean Philippe Vial |
| collection | DOAJ |
| description | The assessment of minimal residual disease (MRD) is increasingly considered to monitor response to therapy in hematological malignancies. In acute myeloblastic leukemia (AML), molecular MRD (mMRD) is possible for about half the patients while multiparameter flow cytometry (MFC) is more broadly available. However, MFC analysis strategies are highly operator-dependent. Recently, new tools have been designed for unsupervised MFC analysis, segregating cell-clusters with the same immunophenotypic characteristics. Here, the Flow-Self-Organizing-Maps (FlowSOM) tool was applied to assess MFC-MRD in 96 bone marrow (BM) follow-up (FU) time-points from 40 AML patients with available mMRD. A reference FlowSOM display was built from 19 healthy/normal BM samples (NBM), then simultaneously compared to the patient’s diagnosis and FU samples at each time-point. MRD clusters were characterized individually in terms of cell numbers and immunophenotype. This strategy disclosed subclones with varying immunophenotype within single diagnosis and FU samples including populations absent from NBM. Detectable MRD was as low as 0.09% in MFC and 0.051% for mMRD. The concordance between mMRD and MFC-MRD was 80.2%. MFC yielded 85% specificity and 69% sensitivity compared to mMRD. Unsupervised MFC is shown here to allow for an easy and robust assessment of MRD, applicable also to AML patients without molecular markers. |
| first_indexed | 2024-03-09T05:34:23Z |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T05:34:23Z |
| publishDate | 2021-02-01 |
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| series | Cancers |
| spelling | doaj.art-6242daf37db64d71bc57318f500920ff2023-12-03T12:29:55ZengMDPI AGCancers2072-66942021-02-0113462910.3390/cancers13040629Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid LeukemiaJean Philippe Vial0Nicolas Lechevalier1Francis Lacombe2Pierre-Yves Dumas3Audrey Bidet4Thibaut Leguay5François Vergez6Arnaud Pigneux7Marie C. Béné8Hematology Biology, Flow Cytometry, Bordeaux University Hospital, 33600 Pessac, FranceHematology Biology, Flow Cytometry, Bordeaux University Hospital, 33600 Pessac, FranceHematology Biology, Flow Cytometry, Bordeaux University Hospital, 33600 Pessac, FranceService d’Hématologie Clinique et de Thérapie Cellulaire, Bordeaux University Hospital, 33600 Pessac, FranceHematology Biology, Molecular Hematology, Bordeaux University Hospital, 33600 Pessac, FranceService d’Hématologie Clinique et de Thérapie Cellulaire, Bordeaux University Hospital, 33600 Pessac, FranceHematology Biology, IUCT Oncopôle, Toulouse University Hospital, 31000 Toulouse, FranceService d’Hématologie Clinique et de Thérapie Cellulaire, Bordeaux University Hospital, 33600 Pessac, FranceHematology Biology, Nantes University Hospital, 44000 Nantes, FranceThe assessment of minimal residual disease (MRD) is increasingly considered to monitor response to therapy in hematological malignancies. In acute myeloblastic leukemia (AML), molecular MRD (mMRD) is possible for about half the patients while multiparameter flow cytometry (MFC) is more broadly available. However, MFC analysis strategies are highly operator-dependent. Recently, new tools have been designed for unsupervised MFC analysis, segregating cell-clusters with the same immunophenotypic characteristics. Here, the Flow-Self-Organizing-Maps (FlowSOM) tool was applied to assess MFC-MRD in 96 bone marrow (BM) follow-up (FU) time-points from 40 AML patients with available mMRD. A reference FlowSOM display was built from 19 healthy/normal BM samples (NBM), then simultaneously compared to the patient’s diagnosis and FU samples at each time-point. MRD clusters were characterized individually in terms of cell numbers and immunophenotype. This strategy disclosed subclones with varying immunophenotype within single diagnosis and FU samples including populations absent from NBM. Detectable MRD was as low as 0.09% in MFC and 0.051% for mMRD. The concordance between mMRD and MFC-MRD was 80.2%. MFC yielded 85% specificity and 69% sensitivity compared to mMRD. Unsupervised MFC is shown here to allow for an easy and robust assessment of MRD, applicable also to AML patients without molecular markers.https://www.mdpi.com/2072-6694/13/4/629acute myeloid leukemiamolecular markersmultiparameter flow cytometryminimal/measurable residual diseaseunsupervised analysisFlowSOM |
| spellingShingle | Jean Philippe Vial Nicolas Lechevalier Francis Lacombe Pierre-Yves Dumas Audrey Bidet Thibaut Leguay François Vergez Arnaud Pigneux Marie C. Béné Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid Leukemia Cancers acute myeloid leukemia molecular markers multiparameter flow cytometry minimal/measurable residual disease unsupervised analysis FlowSOM |
| title | Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid Leukemia |
| title_full | Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid Leukemia |
| title_fullStr | Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid Leukemia |
| title_full_unstemmed | Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid Leukemia |
| title_short | Unsupervised Flow Cytometry Analysis Allows for an Accurate Identification of Minimal Residual Disease Assessment in Acute Myeloid Leukemia |
| title_sort | unsupervised flow cytometry analysis allows for an accurate identification of minimal residual disease assessment in acute myeloid leukemia |
| topic | acute myeloid leukemia molecular markers multiparameter flow cytometry minimal/measurable residual disease unsupervised analysis FlowSOM |
| url | https://www.mdpi.com/2072-6694/13/4/629 |
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