The immunophenotypic landscape of newly diagnosed acute myeloid leukemia: Associations with genotype and outcomes
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.
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BibTeX
@article{mocking2026immunophenotypic,
title = {{The immunophenotypic landscape of newly diagnosed acute myeloid leukemia: Associations with genotype and outcomes}},
author = {Tim R. Mocking and Tom Reuvekamp and Lukas H. Haaksma and Eirini Papavasileiou and Angèle Kelder and Willemijn J. Scholten and Dimitri A. Breems and Thomas Fischer and Bjørn T. Gjertsen and Laimonas Griškevičius and Gunnar Juliusson and Johan A. Maertens and Markus G. Manz and Thomas Pabst and Jakob R. Passweg and Kimmo Porkka and Jeroen J.W.M. Janssen and Patrycja Gradowska and Bob Löwenberg and Gert J. Ossenkoppele and Arjan A. van de Loosdrecht and David C. de Leeuw and Jacqueline Cloos and Peter J.M. Valk and Costa Bachas},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117762},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03143-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The immunophenotypic landscape of newly diagnosed acute myeloid leukemia: Associations with genotype and outcomes
AU - Tim R. Mocking
AU - Tom Reuvekamp
AU - Lukas H. Haaksma
AU - Eirini Papavasileiou
AU - Angèle Kelder
AU - Willemijn J. Scholten
AU - Dimitri A. Breems
AU - Thomas Fischer
AU - Bjørn T. Gjertsen
AU - Laimonas Griškevičius
AU - Gunnar Juliusson
AU - Johan A. Maertens
AU - Markus G. Manz
AU - Thomas Pabst
AU - Jakob R. Passweg
AU - Kimmo Porkka
AU - Jeroen J.W.M. Janssen
AU - Patrycja Gradowska
AU - Bob Löwenberg
AU - Gert J. Ossenkoppele
AU - Arjan A. van de Loosdrecht
AU - David C. de Leeuw
AU - Jacqueline Cloos
AU - Peter J.M. Valk
AU - Costa Bachas
PY - 2026
DA - 2026/10/12
JO - iScience
DO - 10.1016/j.isci.2026.117762
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03143-3
AB - 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.
SN - 2589-0042
ER -