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

Roos Houtsma, Nisha K van der Meer, Kees Meijer, Linde Morsink, Shanna M Hogeling, Carolien Woolthuis, Emanuele Ammatuna, Marije Nijk, Bauke de Boer, Gerwin Huls, Andre B Mulder, Jan Jacob Schuringa*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    6 Citations (Scopus)
    95 Downloads (Pure)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)2129-2143
    Number of pages15
    Journal-
    Volume6
    Issue number7
    Early online date20-Sept-2021
    DOIs
    Publication statusPublished - 12-Apr-2022

    Keywords

    • ACUTE MYELOID-LEUKEMIA
    • MINIMAL RESIDUAL DISEASE
    • CELL TRANSPLANTATION
    • TRANSCRIPTOMICS
    • HETEROGENEITY
    • PROTEOMICS
    • RELAPSE
    • RISK

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