The multiplex crosstalk between non-coding RNAs, programmed cell death and related mechanisms: a dynamic duo in hematological malignancies.

Hematological malignancies, including leukemia, lymphoma, and multiple myeloma (MM), are cancers originating in the hematopoietic system, characterized by diverse pathogenesis and clinical features. Non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long non-coding RNAs, play critical roles in regulating gene expression and influencing cell fate. Accumulating evidence indicates that ncRNAs are key modulators of programmed cell death (PCD) pathways, affecting tumor development, progression, and drug resistance in these malignancies. PCD, a precisely programmed and regulated cell death process, is vital for maintaining tissue homeostasis and preventing the proliferation of dangerous cells. NcRNAs are implicated in the primary mechanisms underlying the development of drug resistance. The evasion of PCD is a hallmark of cancer, and ncRNAs can significantly impact these pathways, with dysregulation observed across leukemia, lymphoma, and myeloma, influencing PCD pathways and clinical outcomes. Understanding the ncRNA-PCD interplay is crucial for developing novel therapeutic strategies and improving patient outcomes. This review explores the functions, regulatory mechanisms, and potential applications of ncRNAs in modulating PCD in hematological malignancies, particularly leukemias, providing insights for future anti-tumor therapies.