Immune profiles in acute myeloid leukemia bone marrow associate with patient age, T-cell receptor clonality, and survival

Author:

Brück Oscar123ORCID,Dufva Olli123ORCID,Hohtari Helena12ORCID,Blom Sami4,Turkki Riku4ORCID,Ilander Mette12ORCID,Kovanen Panu5,Pallaud Celine6,Ramos Pedro Marques6,Lähteenmäki Hanna12,Välimäki Katja4,El Missiry Mohamed12,Ribeiro Antonio4,Kallioniemi Olli47ORCID,Porkka Kimmo123ORCID,Pellinen Teijo4ORCID,Mustjoki Satu1238ORCID

Affiliation:

1. Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland;

2. Translational Immunology Research Program, University of Helsinki, Helsinki, Finland;

3. iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland;

4. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland;

5. Department of Pathology, HUSLAB and Haartman Institute, Helsinki University Hospital, University of Helsinki, Helsinki, Finland;

6. Novartis Pharmaceuticals, Basel, Switzerland;

7. Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institutet, Solna, Sweden; and

8. Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland

Abstract

Abstract The immunologic microenvironment in various solid tumors is aberrant and correlates with clinical survival. Here, we present a comprehensive analysis of the immune environment of acute myeloid leukemia (AML) bone marrow (BM) at diagnosis. We compared the immunologic landscape of formalin-fixed paraffin-embedded BM trephine samples from AML (n = 69), chronic myeloid leukemia (CML; n = 56), and B-cell acute lymphoblastic leukemia (B-ALL) patients (n = 52) at diagnosis to controls (n = 12) with 30 immunophenotype markers using multiplex immunohistochemistry and computerized image analysis. We identified distinct immunologic profiles specific for leukemia subtypes and controls enabling accurate classification of AML (area under the curve [AUC] = 1.0), CML (AUC = 0.99), B-ALL (AUC = 0.96), and control subjects (AUC = 1.0). Interestingly, 2 major immunologic AML clusters differing in age, T-cell receptor clonality, and survival were discovered. A low proportion of regulatory T cells and pSTAT1+cMAF− monocytes were identified as novel biomarkers of superior event-free survival in intensively treated AML patients. Moreover, we demonstrated that AML BM and peripheral blood samples are dissimilar in terms of immune cell phenotypes. To conclude, our study shows that the immunologic landscape considerably varies by leukemia subtype suggesting disease-specific immunoregulation. Furthermore, the association of the AML immune microenvironment with clinical parameters suggests a rationale for including immunologic parameters to improve disease classification or even patient risk stratification.

Publisher

American Society of Hematology

Subject

Hematology

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