ABSTRACT
ABSTRACT Background: Cytokines are key immune mediators in physiological and disease processes, whose increased levels have been associated with the physiopathology of hematopoietic malignancies, such as myeloproliferative neoplasms. Methods: This study examined the plasma cytokine profiles of patients with essential thrombocythemia, primary myelofibrosis, polycythemia vera and of healthy subjects, and analyzed correlations with JAK2 V617F status and clinical-hematological parameters. Results: The proinflammatory cytokine levels were increased in myeloproliferative neoplasm patients, and the presence of the JAK2 V617F mutation was associated with high IP-10 levels in primary myelofibrosis patients. Conclusions: Essential thrombocythemia, primary myelofibrosis, and polycythemia vera patients exhibited different patterns of cytokine production, as revealed by cytokine network correlations. Together, these findings suggest that augmented cytokine levels are associated with the physiopathology of myeloproliferative neoplasms.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Cytokines , Janus Kinase 2 , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative , Inflammation , Myeloproliferative Disorders , NeoplasmsABSTRACT
As neoplasias mieloproliferativas crônicas cromossomo Filadélfia negativas são doenças hematológicas clonais que se caracterizam pela independência ou pela hipersensibilidade dos progenitores hematopoiéticos às citocinas. Os mecanismos celulares e moleculares envolvidos na fisiopatologia das neoplasias mieloproliferativas crônicas ainda não estão totalmente esclarecidos. Achados fisiopatológicos relevantes para as neoplasias mieloproliferativas crônicas estão associados às alterações genéticas como, por exemplo, a mutação somática no gene que codifica o JAK2 (JAK2V617F). A desregulação do processo de morte celular programada, denominada apoptose, parece participar da patogênese dessas desordens. Sabe-se que a desregulação da expressão dos genes pró- e antiapoptóticos promove a resistência das células à apoptose, culminando com o acúmulo das células mieloides e estabelecendo a neoplasia. Esta revisão enfocou as alterações na regulação da apoptose em neoplasias mieloproliferativas crônicas e a importância da melhor compreensão desse mecanismo para o desenvolvimento de novas terapias para essas doenças.
Philadelphia-chromosome negative chronic myeloproliferative neoplasms are clonal hematologic diseases characterized by hematopoietic progenitor independence from or hypersensitivity to cytokines. The cellular and molecular mechanisms involved in the pathophysiology of myeloproliferative neoplasms have not yet been fully clarified. Pathophysiologic findings relevant for myeloproliferative neoplasms are associated with genetic alterations, such as, somatic mutation in the gene that codifies JAK-2 (JAK V617F). Deregulation of the process of programmed cellular death, called apoptosis, seems to participate in the pathogenesis of these disorders. It is known that expression deregulation of pro- and anti-apoptotic genes promotes cell resistance to apoptosis, culminating with the accumulation of myeloid cells and establishing neoplasms. This review will focus on the alterations in apoptosis regulation in myeloproliferative neoplasms, and the importance of a better understanding of this mechanism for the development of new therapies for these diseases.