Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?

SIMPLE SUMMARY: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy arising from the aberrant proliferation of immature T-cell progenitors. Despite improved insights in genetic and biological characteristics of T-ALL, clinical therapy has remained largely similar. Recent studies have shown that leukemia-initiating cells (LICs) and leukemic niches play major roles in the initiation and progression of T-ALL, thus, facilitating the development of targeted therapies. This review provides a broad overview of the recent discoveries on LICs and leukemic niches in the context of T-ALL, with a particular focus on the current precision medicine. ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of hematological malignancy characterized by its high heterogeneity and potentially life-threatening clinical features. Despite the advances in risk stratification and therapeutic management of T-ALL, patients often suffer from treatment failure and chemotherapy-induced toxicity, calling for greater efforts to improve therapeutic efficacy and safety in the treatment of T-ALL. During the past decades, increasing evidence has shown the indispensable effects of leukemia-initiating cells (LICs) and leukemic niches on T-ALL initiation and progression. These milestones greatly facilitate precision medicine by interfering with the pathways that are associated with LICs and leukemic niches or by targeting themselves directly. Most of these novel agents, either alone or in combination with conventional chemotherapy, have shown promising preclinical results, facilitating them to be further evaluated under clinical trials. In this review, we summarize the latest discoveries in LICs and leukemic niches in terms of T-ALL, with a particular highlight on the current precision medicine. The challenges and future prospects are also discussed.