The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies

Abstract

The microenvironment that surrounds a tumor, in addition to the tumor itself, plays an important role in the onset of resistance to molecularly targeted therapies. Cancer cells and their microenvironment interact closely between them by means of a molecular communication that mutually influences their biological characteristics and behavior. Leukemia cells regulate the recruitment, activation and program of the cells of the surrounding microenvironment, including those of the immune system. Studies on the interactions between the bone marrow (BM) microenvironment and Acute Lymphoblastic Leukemia (ALL) cells have opened a scenario of potential therapeutic targets which include cytokines and their receptors, signal transduction networks, and hypoxia-related proteins. Hypoxia also enhances the formation of new blood vessels, and several studies show how angiogenesis could have a key role in the pathogenesis of ALL. Knowledge of the molecular mechanisms underlying tumor-microenvironment communication and angiogenesis could contribute to the early diagnosis of leukemia and to personalized molecular therapies. This article is part of a Special Issue entitled: Innovative Multi-Disciplinary Approaches for Precision Studies in Leukemia edited by Sandra Marmiroli (University of Modena and Reggio Emilia, Modena, Italy) and Xu Huang (University of Glasgow, Glasgow, United Kingdom).

Construction of three‐gene‐based prognostic signature and analysis of immune cells infiltration in children and young adults with B‐acute lymphoblastic leukemia

“…The tumor microenvironment (TME) was an important factor in the development and progression of ALL, and immune cell infiltration was a component of TME (Cencini et al, 2021 ; Pastorczak et al, 2021 ; Simioni et al, 2021 ; Witkowski et al, 2020 ). For a better understanding the reasons contributing to poor prognosis, we evaluated the levels of 22 tumor‐infiltrating immune cells via CIBERSORT analysis.…”

Circulating Biomarkers Associated with the Diagnosis and Prognosis of B-Cell Progenitor Acute Lymphoblastic Leukemia

“…LSC block differentiation and can proliferate in PB, BM, and other organs. [ 1 , 6 , 7 , 8 , 35 , 36 ]. Moreover, their rapid growth leads to accumulation that may interfere with the suppression of normal hematopoiesis [ 8 , 9 ].…”

High-throughput formulation of reproducible 3D cancer microenvironments for drug testing in myelogenous leukemia

“…In general, the development of leukemic 3D microenvironment models remains challenging due to the intrinsic complexity of the leukemic CME which includes a variety of bone marrow cells and signaling pathways (Simioni et al, 2021). For example, it has been previously shown that the myeloid malignant cells can induce extensive niche remodeling when growing in the bone marrow and disrupt the normal perivascular niche by reducing CXCL12 production (Colmone et al, 2008).…”