Programmed Cell Death Deregulation in BCR-ABL1-Negative Myeloproliferative Neoplasms

Abstract

BCR-ABL1-negative myeloproliferative neoplasms are classically represented by primary myelofibrosis, polycythemia vera, and essential thrombocythemia. These entities are stem cell-derived clonal disorders characterized by hematopoietic progenitor autonomy or hypersensitivity to cytokines, most of them presenting mutations in Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL). Deregulation of pro-and antiapoptotic genes is also claimed as an important mechanism involved in cell resistance to cell death and accumulation of myeloid cells in myeloproliferative neoplasms. Apoptosis, as one of the best-characterized types of programmed cell death, has a clear role in hematopoiesis control. However, the exact pathways affected in BCR-ABL1-negative myeloproliferative neoplasms have not yet been fully clarified. This chapter will explore the modifications affecting programmed cell death pathways involved in myeloid proliferation and how these alterations might be exploited in single or combined targeted therapeutic strategies.

Neutrophil Death in Myeloproliferative Neoplasms: Shedding More Light on Neutrophils as a Pathogenic Link to Chronic Inflammation

“…Tognon et al [78], Mambet et al [19] as well as Diaconu et al [155] provided an overview of dysregulation process of programmed cell death by apoptosis in Ph-MPN. The literature they presented showed the importance of both intrinsic and extrinsic apoptotic pathways in the pathogenesis of MPN.…”