The triad inflammation-microenvironment-tumor initiating cells in leukemia progression

Inflammation, a regulatory mechanism crucial for the homeostasis and maintenance of the hematopoietic system, is capable of playing pathogenic roles that ultimately cooperate in malignant progression. Its continuous and multilevel interplay with inducing microenvironments and genetically aberrant leukemia initiating cells within the bone marrow, can create a stable triad structure present from the earliest stages of tumor emergence. This review aims to discuss the most recent advances in the essential functions of inflammatory signals in both, steady-state and malignant hematopoiesis. By shedding more light on the mechanisms underlying the expansion and maintenance of malignant primitive cells under aberrant activating microenvironments, it may contribute to a comprehensive understanding of the leukemia pathobiology. New strategies to intervene the dynamic intercommunication between components of the inflammation-microenvironment-leukemia initiating cell triad would be of crucial relevance for an integral control of hematological malignancies.