TY - JOUR
T1 - CombiFlow
T2 - combinatorial AML-specific plasma membrane expression profiles allow longitudinal tracking of clones
AU - Houtsma, Roos
AU - van der Meer, Nisha K
AU - Meijer, Kees
AU - Morsink, Linde
AU - Hogeling, Shanna M
AU - Woolthuis, Carolien
AU - Ammatuna, Emanuele
AU - Nijk, Marije
AU - de Boer, Bauke
AU - Huls, Gerwin
AU - Mulder, Andre B
AU - Schuringa, Jan Jacob
N1 - Copyright © 2021 American Society of Hematology.
PY - 2022/4/12
Y1 - 2022/4/12
N2 - 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.
AB - 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.
KW - ACUTE MYELOID-LEUKEMIA
KW - MINIMAL RESIDUAL DISEASE
KW - CELL TRANSPLANTATION
KW - TRANSCRIPTOMICS
KW - HETEROGENEITY
KW - PROTEOMICS
KW - RELAPSE
KW - RISK
U2 - 10.1182/bloodadvances.2021005018
DO - 10.1182/bloodadvances.2021005018
M3 - Article
C2 - 34543390
SN - 0000-0000
VL - 6
SP - 2129
EP - 2143
JO - -
JF - -
IS - 7
ER -