Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor prognosis and limited treatment options. Here we provide a comprehensive census of the bone marrow immune microenvironment in adult and pediatric patients with AML. We characterize unique inflammation signatures in a subset of AML patients, associated with inferior outcomes. We identify atypical B cells, a dysfunctional B-cell subtype enriched in patients with high-inflammation AML, as well as an increase in CD8GZMK and regulatory T cells, accompanied by a reduction in T-cell clonal expansion. We derive an inflammation-associated gene score (iScore) that associates with poor survival outcomes in patients with AML. Addition of the iScore refines current risk stratifications for patients with AML and may enable identification of patients in need of more aggressive treatment. This work provides a framework for classifying patients with AML based on their immune microenvironment and a rationale for consideration of the inflammatory state in clinical settings.
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http://dx.doi.org/10.1038/s43018-022-00480-0 | DOI Listing |
Blood
January 2025
The Medical College of Wisconsin Inc., Milwaukee, Wisconsin, United States.
Recent advances in acute myeloid leukemia (AML) come from studies investigating younger (age<60 years) adults or older (age≥75 years) or less fit adults. Uncertainty exists for the management of otherwise healthy adults with AML in their 60s and 70s, which also represents a significant proportion of AML cases. We discuss current considerations in older, fit adults with AML including determination of fitness, what factors beyond fitness should be assessed, and finally what challenges and innovations lie ahead to improve outcomes for these patients.
View Article and Find Full Text PDFSci Immunol
January 2025
Irving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA.
Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded CD8 cytotoxic T lymphocytes with in vitro specificity for patient-matched AML.
View Article and Find Full Text PDFBlood Adv
January 2025
The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States.
Results following hematopoietic stem cell transplantation (HSCT) for TP53-mutated myeloid malignancies are disappointing. Several HSCT centers decline to perform HSCT for patients with TP53 mutation because of poor outcomes. In this study, we analyzed 240 patients with TP53-mutated myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that underwent HSCT.
View Article and Find Full Text PDFRev Med Chil
September 2024
Departamento de Hematología, Hospital Sótero del Río, Santiago, Chile.
Unlabelled: Acute myeloid leukemia (AML) is the most frequent type of leukemia in adults and has a high mortality burden. Patients over 60 years of age infrequently receive high-intensity chemotherapy.
Aim: To describe the clinical characteristics and evaluate the survival in patients with AML, focusing on patients over 60 years.
Diseases
January 2025
Department of Haematology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece.
T cells, as integral components of the adaptive immune system, recognize diverse antigens through unique T cell receptors (TCRs). To achieve this, during T cell maturation, the thymus generates a wide repertoire of TCRs. This is essential for understanding cancer evolution, progression, and the efficacy of immunotherapies.
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