Acute myeloid leukemia: Is it t time?

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 cytope-nia and immunodeficiency. This review describes how the AML microenvironment influences lym-phoid 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 func-tion, 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 sug-gest and summarize current immunotherapeutic strategies and challenges to overcome these anom-alies to improve the anti-leukemic immune response and the clinical outcome of patients.