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Non coding RNAs (ncRNAs) have emerged as regulators of human carcinogenesis by affecting the expression of key tumor suppressor genes and oncogenes. They are divided into short and long ncRNAs, according to their length. Circular RNAs (circRNAs) are included in the second group and were recently discovered as being originated by back-splicing, joining either single or multiple exons, or exons with retained introns. The human  Plasmacytoma Variant Translocation 1  ( PVT1 ) gene maps on the long arm of chromosome 8 (8q24) and encodes for 52 ncRNAs variants, including 26 linear and 26 circular isoforms, and 6 microRNAs.  PVT1  genomic locus is 54 Kb downstream to  MYC  and several interactions have been described among these two genes, including a feedback regulatory mechanism.  MYC -independent functions of  PVT1 / circPVT1  have been also reported, especially in the regulation of immune responses. We here review and discuss the role of both  PVT1  and  circPVT1  in the hematopoietic system. No information is currently available concerning their transforming ability in hematopoietic cells. However, present literature supports their cooperation with a more aggressive and/or undifferentiated cell phenotype, thus contributing to cancer progression.  PVT1 / circPVT1  upregulation through genomic amplification or rearrangements and/or increased transcription, provides a proliferative advantage to malignant cells in acute myeloid leukemia, acute promyelocytic leukemia, Burkitt lymphoma, multiple myeloma (linear  PVT1 ) and acute lymphoblastic leukemia ( circPVT1 ). In addition,  PVT1  and  circPVT1  regulate immune responses: the overexpression of the linear form in myeloid derived suppressor cells induced immune tolerance in preclinical tumor models and  circPVT1  showed immunosuppressive properties in myeloid and lymphoid cell subsets. Overall, these recent data on  PVT1  and  circPVT1  functions in hematological malignancies and immune responses reflect two faces of the same coin: involvement in cancer progression by promoting a more aggressive phenotype of malignant cells and negative regulation of the immune system as a novel potential therapy-resistance mechanism.

Linear and circular PVT1 in hematological malignancies and immune response: two faces of the same coin