The immunophenotypic landscape of newly diagnosed acute myeloid leukemia: Associations with genotype and outcomes
Year: 2026
Type: article
Study design: Observational Study
Abstract: Despite widespread immunophenotyping in acute myeloid leukemia (AML), its immunophenotypic heterogeneity remains incompletely understood. Here, we applied state-of-the-art computational modeling to >50 million single cells from diagnostic bone marrow aspirates of 502 AML patients. Jointly modeling leukemic and non-malignant cells, we identified seven patient clusters with distinct immunophenotypic signatures. These clusters showed strong concordance with recurrent mutations, including NPM1 , IDH1/IDH2 , CEBPA , and t(8;21)(q22;q22); RUNX1-RUNX1T1 fusions, and enabled accurate prediction of genomic subgroups. Although these immunophenotypic signatures were not associated with therapy responses, loss of HLA-DR expression on leukemic blasts at diagnosis was independently associated with inferior outcomes in patients with chromatin-spliceosome mutations. In addition, we identified an immunophenotypic patient cluster comprising ∼11% of patients characterized by significant bone marrow lymphocyte enrichment where outcomes diverged depending on genetic risk. Together, these findings provide a comprehensive single-cell characterization of AML bone marrow and reveal clinically relevant genotype-phenotype relationships.
Source: iScience
Authors: Tim R. Mocking, Tom Reuvekamp, Lukas H. Haaksma, Eirini Papavasileiou, Angèle Kelder, Willemijn J. Scholten, Dimitri A. Breems, Thomas Fischer, Bjørn T. Gjertsen, Laimonas Griškevičius, Gunnar Juliusson, Johan A. Maertens, Markus G. Manz, Thomas Pabst, Jakob R. Passweg, Kimmo Porkka, Jeroen J.W.M. Janssen, Patrycja Gradowska, Bob Löwenberg, Gert J. Ossenkoppele, Arjan A. van de Loosdrecht, David C. de Leeuw, Jacqueline Cloos, Peter J.M. Valk, Costa Bachas
Institutions: Amsterdam University Medical Centers, Cancer Center Amsterdam, Ziekenhuis aan de Stroom, University Hospital Magdeburg, Otto-von-Guericke-Universität Magdeburg, Haukeland University Hospital, Vilnius University, Vilnius University Hospital Santariskiu Klinikos, Skåne University Hospital, Universitair Ziekenhuis Leuven, University Hospital Zurich, Swiss Group For Clinical Cancer Research, University Hospital of Bern, University Hospital of Basel, Helsinki University Hospital, Radboud University Medical Center, Erasmus MC, Hovon, Erasmus MC Cancer Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,240
OpenAlex ID: W7221555811