Specialized Intercellular Communications via Tunnelling Nanotubes in Acute and Chronic Leukemia

Simple Summary Tunneling nanotubes (TNTs) are cytoplasmic channels which regulate the contacts between cells and allow the transfer of several elements, including ions, mitochondria, microvesicles, exosomes, lysosomes, proteins, and microRNAs. Through this transport, TNTs are implicated in different physiological and pathological phenomena, such as immune response, cell proliferation and differentiation, embryogenesis, programmed cell death, and angiogenesis. TNTs can promote cancer progression, transferring substances capable of altering apoptotic dynamics, modifying the metabolism and energy balance, inducing changes in immunosurveillance, or affecting the response to chemotherapy. In this review, we evaluated their influence on hematologic malignancies' progression and resistance to therapies, focusing on acute and chronic myeloid and acute lymphoid leukemia. Effectual cell-to-cell communication is essential to the development and differentiation of organisms, the preservation of tissue tasks, and the synchronization of their different physiological actions, but also to the proliferation and metastasis of tumor cells. Tunneling nanotubes (TNTs) are membrane-enclosed tubular connections between cells that carry a multiplicity of cellular loads, such as exosomes, non-coding RNAs, mitochondria, and proteins, and they have been identified as the main participants in healthy and tumoral cell communication. TNTs have been described in numerous tumors in in vitro, ex vivo, and in vivo models favoring the onset and progression of tumors. Tumor cells utilize TNT-like membranous channels to transfer information between themselves or with the tumoral milieu. As a result, tumor cells attain novel capabilities, such as the increased capacity of metastasis, metabolic plasticity, angiogenic aptitude, and chemoresistance, promoting tumor severity. Here, we review the morphological and operational characteristics of TNTs and their influence on hematologic malignancies' progression and resistance to therapies, focusing on acute and chronic myeloid and acute lymphoid leukemia. Finally, we examine the prospects and challenges for TNTs as a therapeutic approach for hematologic diseases by examining the development of efficient and safe drugs targeting TNTs.