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<p>Acute myeloid leukemia (AML) is a blood cancer with poor survival outcomes. Acute respiratory failure frequently occurs due to leukemia infiltration of the lungs. Underlying mechanisms remain unexplored and therapeutic interventions remain empiric. Here we map the AML lung microenvironment at spatial and single-cell resolution. We show that extensive remodeling is coupled with inflammation and impaired tissue integrity and function. Steroid treatment significantly reduces AML burden and lung infiltration, improving oxygenation and pulmonary function. As a mechanistic correlate, the S-type lectin Lgals9 is triggered by inflammation and mediates cell–cell interactions within infiltrated lungs. Also, the alarmin IL-33 and its receptor (IL-1RL1) are involved in cell–cell interactions within the leukemic lung microenvironment. Targeting either the <i>Lgals9</i> or IL-33 axis significantly decreases overall AML burden and lung infiltration through effects on both the immune microenvironment and AML cells. Our studies delineate pulmonary infiltration phenotypes in acute leukemia, enabling new treatment strategies.</p>

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Inflammatory immune modulators of AML lung infiltration and respiratory failure

  • 期刊论文

  • 发表日期：

    2026年6月29日

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  • Varvara Paraskevopoulou,
  • Ziyan Lin,
  • Marta Casado-Pelaez,
  • Daniela Grases,
  • Wafa Al-Santli,
  • Juan Carlos Balandrán,
  • Fang Zhou,
  • Ali Rashidfarrokhi,
  • Michael Cross,
  • Stephen T. Yeung,
  • Konstantinos Ntatsoulis,
  • Tejas Patel,
  • Xufeng Chen,
  • Deedra Nicolet,
  • Marc Escobosa,
  • Eduard Porta,
  • Jennifer J. Trowbridge,
  • Kamal M. Khanna,
  • Thales Papagiannakopoulos,
  • Andre L. Moreira,
  • Rashmi Kanagal-Shamanna,
  • Sanam Loghavi,
  • Aris Tsirigos,
  • Ann-Kathrin Eisfeld,
  • Manel Esteller,
  • Iannis Aifantis

摘要

Acute myeloid leukemia (AML) is a blood cancer with poor survival outcomes. Acute respiratory failure frequently occurs due to leukemia infiltration of the lungs. Underlying mechanisms remain unexplored and therapeutic interventions remain empiric. Here we map the AML lung microenvironment at spatial and single-cell resolution. We show that extensive remodeling is coupled with inflammation and impaired tissue integrity and function. Steroid treatment significantly reduces AML burden and lung infiltration, improving oxygenation and pulmonary function. As a mechanistic correlate, the S-type lectin Lgals9 is triggered by inflammation and mediates cell–cell interactions within infiltrated lungs. Also, the alarmin IL-33 and its receptor (IL-1RL1) are involved in cell–cell interactions within the leukemic lung microenvironment. Targeting either the Lgals9 or IL-33 axis significantly decreases overall AML burden and lung infiltration through effects on both the immune microenvironment and AML cells. Our studies delineate pulmonary infiltration phenotypes in acute leukemia, enabling new treatment strategies.