Acute Myeloid Leukemia: Is It T Time?

SIMPLE SUMMARY: Acute myeloid leukemia (AML) is a cancer characterized by impaired differentiation and excessive expansion of blood progenitor cells leading to their accumulation in the bone marrow and circulation. The aim of this review is to describe how these leukemic cells can influence the immune system, particularly T lymphocytes that originate from the thymus and are involved in cancers’ and infections’ eradication. We focus on the elderly population, as this disease mainly affects people over 60 years-old. We discuss how AML cells can modify T lymphocytes’ production and functions. We also highlight newly developed therapeutic strategies to improve the anti-leukemic immune response and the clinical outcome of patients. ABSTRACT: Acute myeloid leukemia (AML) is a heterogeneous disease driven by impaired differentiation of hematopoietic primitive cells toward myeloid lineages (monocytes, granulocytes, red blood cells, platelets), leading to expansion and accumulation of “stem” and/or “progenitor”-like or differentiated leukemic cells in the bone marrow and blood. AML progression alters the bone marrow microenvironment and inhibits hematopoiesis’ proper functioning, causing sustained cytopenia and immunodeficiency. This review describes how the AML microenvironment influences lymphoid lineages, particularly T lymphocytes that originate from the thymus and orchestrate adaptive immune response. We focus on the elderly population, which is mainly affected by this pathology. We discuss how a permissive AML microenvironment can alter and even worsen the thymic function, T cells’ peripheral homeostasis, phenotype, and functions. Based on the recent findings on the mechanisms supporting that AML induces quantitative and qualitative changes in T cells, we suggest and summarize current immunotherapeutic strategies and challenges to overcome these anomalies to improve the anti-leukemic immune response and the clinical outcome of patients.