New Insights into YES-Associated Protein Signaling Pathways in Hematological Malignancies: Diagnostic and Therapeutic Challenges

SIMPLE SUMMARY: YES-associated protein (YAP) is a co-transcriptional activator that binds to transcriptional factors to increase the rate of transcription of a set of genes, and it can intervene in the onset and progression of different tumors. Most of the data in the literature refer to the effects of the YAP system in solid neoplasms. In this review, we analyze the possibility that YAP can also intervene in hematological neoplasms such as lymphomas, multiple myeloma, and acute and chronic leukemias, modifying the phenomena of cell proliferation and cell death. The possibilities of pharmacological intervention related to the YAP system in an attempt to use its modulation therapeutically are also discussed. ABSTRACT: The Hippo/YES-associated protein (YAP) signaling pathway is a cell survival and proliferation-control system with its main activity that of regulating cell growth and organ volume. YAP operates as a transcriptional coactivator in regulating the onset, progression, and treatment response in numerous human tumors. Moreover, there is evidence suggesting the involvement of YAP in the control of the hematopoietic system, in physiological conditions rather than in hematological diseases. Nevertheless, several reports have proposed that the effects of YAP in tumor cells are cell-dependent and cell-type-determined, even if YAP usually interrelates with extracellular signaling to stimulate the onset and progression of tumors. In the present review, we report the most recent findings in the literature on the relationship between the YAP system and hematological neoplasms. Moreover, we evaluate the possible therapeutic use of the modulation of the YAP system in the treatment of malignancies. Given the effects of the YAP system in immunosurveillance, tumorigenesis, and chemoresistance, further studies on interactions between the YAP system and hematological malignancies will offer very relevant information for the targeting of these diseases employing YAP modifiers alone or in combination with chemotherapy drugs.