Database-Guided Analysis for Immunophenotypic Diagnosis and Follow-Up of Acute Myeloid Leukemia With Recurrent Genetic Abnormalities

Aanei, Carmen-Mariana; Veyrat-Masson, Richard; Selicean, Cristina; Marian, Mirela; Rigollet, Lauren; Tomuleasa, Ciprian; Şerban, Adrian; Cherry, Mohamad; Flandrin-Gresta, Pascale; Tardy, Emmanuelle Tavernier; Guyotat, Denis; Catafal, Lydia Campos

doi:10.3389/fonc.2021.746951

Cited by 7 publications

(6 citation statements)

References 20 publications

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“…Our strategy extends further by allowing the identification of LAIPs even if they are expressed only in a small part of the leukemic population, which are otherwise impossible to detect by conventional methods. Thus, our findings confirm previous observations evidencing that conventional strategies could be significantly improved [ 4 , 20 , 21 , 22 ]. One of the greatest challenges for MFC-MRD assessment is the presence of cell populations expressing the identified LAIPs in healthy or regenerating bone marrow samples [ 8 , 23 ].…”

Section: Discussionsupporting

confidence: 92%

Identification of Leukemia-Associated Immunophenotypes by Databaseguided Flow Cytometry Provides a Highly Sensitive and Reproducible Strategy for the Study of Measurable Residual Disease in Acute Myeloblastic Leukemia

Piñero¹,

Morilla

Gutiérrez

et al. 2022

Cancers

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Background: Multiparametric Flow Cytometry (MFC) is an essential tool to study the involved cell lineages, the aberrant differentiation/maturation patterns and the expression of aberrant antigens in acute myeloid leukemia (AML). The characterization of leukemia-associated immunophenotypes (LAIPs) at the moment of diagnosis is critical to establish reproducible strategies for the study of measurable residual disease using MFC (MFC-MRD). Methods: In this study, we identify and characterize LAIPs by comparing the leukemic populations of 145 AML patients, using the EuroFlow AML/ MDS MFC panel, with six databases of normal myeloid progenitors (MPCs). Principal component analysis was used to identify and characterize the LAIPs, which were then used to generate individual profiles for MFC-MRD monitoring. Furthermore, we investigated the relationship between the expression patterns of LAIPs and the different subtypes of AML. The MFC-MRD study was performed by identifying residual AML populations that matched with the LAIPs at diagnosis. To further validate this approach, the presence of MRD was also assessed by qPCR (qPCR-MRD). Finally, we studied the association between MFC-MRD and progression-free survival (PFS). Results: The strategy used in this study allowed us to describe more than 300 different LAIPs and facilitated the association of specific phenotypes with certain subtypes of AML. The MFC-MRD monitoring based on LAIPs with good/strong specificity was applicable to virtually all patients and showed a good correlation with qPCR-MRD and PFS. Conclusions: The described methodology provides an objective method to identify and characterize LAIPs. Furthermore, it provides a theoretical basis to develop highly sensitive MFC-MRD strategies.

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Section: Discussionsupporting

confidence: 92%

Identification of Leukemia-Associated Immunophenotypes by Databaseguided Flow Cytometry Provides a Highly Sensitive and Reproducible Strategy for the Study of Measurable Residual Disease in Acute Myeloblastic Leukemia

Piñero¹,

Morilla

Gutiérrez

et al. 2022

Cancers

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show abstract

Section: Discussionsupporting

confidence: 92%

“…Our strategy goes further allowing the identification of LAIPs even if they are expressed only in a small part of the leukemic population, which are otherwise impossible to detect by conventional methods. Thus, our findings confirm previous observations evidencing that conventional strategies could be significantly improved [4,[20][21][22] One of the greatest challenges for MFC-MRD assessment is the presence of cell populations expressing the identified LAIPs in healthy or regenerating bone marrow samples [8,23]. Our results confirm these observations even using individual monitoring profiles and database guided analysis for the exclusion of phenotypically normal cells.…”

Section: Discussionsupporting

confidence: 89%

Identification of leukemia-associated immunophenotypes by database-guided flow cytometry provides a highly sensitive and reproducible strategy for the study of measurable residual disease in acute myeloblastic leukemia

Piñero¹,

Morillas²,

Gutiérrez³

et al. 2022

Preprint

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Background: Multiparametric Flow Cytometry (MFC) is an essential tool to study the involved cell lineages, the aberrant differentiation/maturation patterns and the expression of aberrant antigens in acute myeloid leukemia (AML). The characterization of leukemia-associated immunophenotypes (LAIPs) at the moment of diagnosis is critical to establish reproducible strategies for the study of measurable residual disease using MFC (MFC-MRD). Methods: In this study, we identified and characterized LAIPs by comparing the leukemic populations of 145 AML patients, using the EuroFlow AML/ MDS MFC panel, with 6 databases of normal myeloid progenitors (MPCs). Principal component analysis was used to identify and characterize the LAIPs, which were then used to generate individual profiles for MFC-MRD monitoring. Furthermore, we investigated the relationship between the expression patterns of LAIPs and the different subtypes of AML. The MFC-MRD study was performed by identifying residual AML populations that matched with the LAIPs at diagnosis. To further validate this approach, the presence of MRD was also assessed by qPCR (qPCRMRD). Finally, we studied the association between MFC-MRD and progression-free survival (PFS). Results: The strategy used in this study allowed us to describe more than 300 different LAIPs and facilitated the association of specific phenotypes with certain subtypes of AML. The MFC-MRD monitoring based on LAIPs with good/strong specificity was applicable to virtually all patients and showed a good correlation with qPCR-MRD and PFS. Conclusions: The described methodology provides an objective method to identify and characterize LAIPs. Furthermore, it provides a theoretical basis to develop highly sensitive MFC-MRD strategies.

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“…One sample had to be excluded from the analysis due to clotting issues. The sample preparation procedures and the staining strategy were previously described in detail ( 38 , 39 ). The monoclonal antibodies we have used are summarized in Supplementary Table S1 .…”

Section: Methodsmentioning

confidence: 99%

Combined flow cytometry natural killer immunophenotyping and KIR/HLA-C genotyping reveal remarkable differences in acute myeloid leukemia patients, but suggest an overall impairment of the natural killer response

Cianga

Rusu²,

Pavel-Tanasa³

et al. 2023

Front. Med.

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IntroductionNatural killer (NK) cells are key anti-tumor effectors of the innate immunity. Phenotypic differences allow us to discriminate in between three functional stages of maturation, named immature, mature and hypermature that are distinctive in terms of receptor expression, cytokine secretion, cytotoxic properties and organ trafficking. NKs display an impressive repertoire of highly polymorphic germline encoded receptors that can be either activating, triggering the effector’s function, or inhibitory, limiting the immune response. In our study, we have investigated peripheral blood NK cells of acute myeloid leukemia (AML) patients.MethodsThe Killer Immunoglobulin-like receptors (KIRs) and the HLA-C genotypes were assessed, as HLA-C molecules are cognate antigens for inhibitory KIRs.ResultsThe AA mainly inhibitory KIR haplotype was found in a higher proportion in AML, while a striking low frequency of the 2DS3 characterized the mainly activating Bx haplotype. Flow cytometry immunophenotyping evidenced a lower overall count of NK cells in AML versus healthy controls, with lower percentages of the immature and mature subpopulations, but with a markedly increase of the hypermature NKs. The analysis of the KIR2DL1, KIR2DL2, KIR2DL3, KIR3DL1, and NKG2A inhibitory receptors surface expression revealed a remarkable heterogeneity. However, an overall trend for a higher expression in AML patients could be noticed in all maturation subpopulations. Some of the AML patients with complex karyotypes or displaying a FLT3 gene mutation proved to be extreme outliers in terms of NK cells percentages or inhibitory receptors expression.DiscussionWe conclude that while the genetic background investigation in AML offers important pieces of information regarding susceptibility to disease or prognosis, it is flow cytometry that is able to offer details of finesse in terms of NK numbers and phenotypes, necessary for an adequate individual evaluation of these patients.

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Database-Guided Analysis for Immunophenotypic Diagnosis and Follow-Up of Acute Myeloid Leukemia With Recurrent Genetic Abnormalities

Cited by 7 publications

References 20 publications

Identification of Leukemia-Associated Immunophenotypes by Databaseguided Flow Cytometry Provides a Highly Sensitive and Reproducible Strategy for the Study of Measurable Residual Disease in Acute Myeloblastic Leukemia

Identification of Leukemia-Associated Immunophenotypes by Databaseguided Flow Cytometry Provides a Highly Sensitive and Reproducible Strategy for the Study of Measurable Residual Disease in Acute Myeloblastic Leukemia

Identification of leukemia-associated immunophenotypes by database-guided flow cytometry provides a highly sensitive and reproducible strategy for the study of measurable residual disease in acute myeloblastic leukemia

Combined flow cytometry natural killer immunophenotyping and KIR/HLA-C genotyping reveal remarkable differences in acute myeloid leukemia patients, but suggest an overall impairment of the natural killer response

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