CombiFlow: combinatorial AML-specific plasma membrane expression profiles allow longitudinal tracking of clones.

Autor:	Houtsma R; Department of Hematology, and., van der Meer NK; Department of Hematology, and., Meijer K; Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Morsink LM; Department of Hematology, and., Hogeling SM; Department of Hematology, and., Woolthuis CM; Department of Hematology, and., Ammatuna E; Department of Hematology, and., Nijk MT; Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., de Boer B; Department of Hematology, and., Huls G; Department of Hematology, and., Mulder AB; Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Schuringa JJ; Department of Hematology, and.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2022 Apr 12; Vol. 6 (7), pp. 2129-2143.
DOI:	10.1182/bloodadvances.2021005018
Abstrakt:	Acute myeloid leukemia (AML) often presents as an oligoclonal disease whereby multiple genetically distinct subclones can coexist within patients. Differences in signaling and drug sensitivity of such subclones complicate treatment and warrant tools to identify them and track disease progression. We previously identified >50 AML-specific plasma membrane (PM) proteins, and 7 of these (CD82, CD97, FLT3, IL1RAP, TIM3, CD25, and CD123) were implemented in routine diagnostics in patients with AML (n = 256) and myelodysplastic syndrome (n = 33). We developed a pipeline termed CombiFlow in which expression data of multiple PM markers is merged, allowing a principal component-based analysis to identify distinctive marker expression profiles and to generate single-cell t-distributed stochastic neighbor embedding landscapes to longitudinally track clonal evolution. Positivity for one or more of the markers after 2 courses of intensive chemotherapy predicted a shorter relapse-free survival, supporting a role for these markers in measurable residual disease (MRD) detection. CombiFlow also allowed the tracking of clonal evolution in paired diagnosis and relapse samples. Extending the panel to 36 AML-specific markers further refined the CombiFlow pipeline. In conclusion, CombiFlow provides a valuable tool in the diagnosis, MRD detection, clonal tracking, and understanding of clonal heterogeneity in AML. (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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