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<p>In a mouse model of FGFR1-driven leukemia, we demonstrated a role for circulating non-conventional monocyte-derived macrophages in the peripheral blood, which suppressed T-cell function and promoted leukemogenesis. A single cell RNA sequencing (scRNA-Seq) analysis of these leukemia-associated macrophages (LAMs) identified LAM-specific dysregulation of gene expression associated with leukemogenesis. Based on the top markers identified in these LAMs, we generated a LAM score based on the expression levels of a 32 gene signature. This scoring system was then applied to the transcriptomic data from a cohort of 838 newly diagnosed patients treated on Alliance/CALGB protocols, who were similarly treated with intensive cytarabine/daunorubicin-based chemotherapy on the CALGB/Alliance for the Clinical Trials in Oncology protocol. Patients were subclassified as those with high and low LAM scores. Patients with a high LAM score had shorter overall survival, disease-free survival and event-free survival compared to those with a low LAM score. We also noted a strong association of <i>FLT3-ITD</i>, <i>RUNX1</i> and <i>TP53</i> mutations with high LAM scores. Applying the LAM score to the current European Leukemia Network risk group criteria, independent prognostic implications and a refined prognostic significance of each subgroup were provided, indicating the value of including immune microenvironment data into AML risk stratification.</p>

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A gene signature derived from leukemia associated macrophages provides a compelling risk stratification for human AML patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月29日

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  • Deedra Nicolet,
  • Ting Zhang,
  • Christopher J. Walker,
  • Justice Ameyi,
  • Stephanie F. Mori,
  • Xuexiu Fang,
  • Litao Zhang,
  • Jorge Cortes,
  • Catherine C. Hedrick,
  • John K. Cowell,
  • Ann-Kathrin Eisfeld,
  • Tianxiang Hu

摘要

In a mouse model of FGFR1-driven leukemia, we demonstrated a role for circulating non-conventional monocyte-derived macrophages in the peripheral blood, which suppressed T-cell function and promoted leukemogenesis. A single cell RNA sequencing (scRNA-Seq) analysis of these leukemia-associated macrophages (LAMs) identified LAM-specific dysregulation of gene expression associated with leukemogenesis. Based on the top markers identified in these LAMs, we generated a LAM score based on the expression levels of a 32 gene signature. This scoring system was then applied to the transcriptomic data from a cohort of 838 newly diagnosed patients treated on Alliance/CALGB protocols, who were similarly treated with intensive cytarabine/daunorubicin-based chemotherapy on the CALGB/Alliance for the Clinical Trials in Oncology protocol. Patients were subclassified as those with high and low LAM scores. Patients with a high LAM score had shorter overall survival, disease-free survival and event-free survival compared to those with a low LAM score. We also noted a strong association of FLT3-ITD, RUNX1 and TP53 mutations with high LAM scores. Applying the LAM score to the current European Leukemia Network risk group criteria, independent prognostic implications and a refined prognostic significance of each subgroup were provided, indicating the value of including immune microenvironment data into AML risk stratification.