Philadelphia-negative chronic myeloproliferative neoplasms

Abstract

Chronic myeloproliferative diseases without the Philadelphia chromosome marker (Ph-), although first described 60 years ago, only became the subject of interest after the turn of the millennium. In 2001, the World Health Organization (WHO) defined the classification of this group of diseases and in 2008 they were renamed myeloproliferative neoplasms based on morphological, cytogenetic and molecular features. In 2005, the identification of a recurrent molecular abnormality characterized by a gain of function with a mutation in the gene encoding Janus kinase 2 (JAK2) paved the way for greater knowledge of the pathophysiology of myeloproliferative neoplasms. The JAK2 mutation is found in 90-98% of polycythemia vera and in about 50% essential thrombocytosis and primary myelofibrosis. In addition to the JAK2 mutation, other mutations involving TET2 (ten-eleven translocation), LNK (a membrane-bound adaptor protein); IDH1/2 (isocitrate dehydrogenase 1/2 enzyme); ASXL1 (additional sex combs-like 1) genes were found in myeloproliferative neoplasms thus showing the importance of identifying molecular genetic alterations to confirm diagnosis, guide treatment and improve our understanding of the biology of these diseases. Currently, polycythemia vera, essential thrombocytosis, myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia and mastocytosis are included in this group of myeloproliferative neoplasms, but are considered different situations with individualized diagnostic methods and treatment. This review updates pathogenic aspects, molecular genetic alterations, the fundamental criteria for diagnosis and the best approach for each of these entities.

Putative Role of Neutrophil Extracellular Trap Formation in Chronic Myeloproliferative Neoplasms

“…Phnegative MPN neoplasms may be clinically presented as one of three classical subtypes, namely essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). PV is marked by absolute erythrocytosis, i.e., an increase in red cell mass, and increased numbers of leukocytes and platelets ("trilineage growth"), whilst ET is characterized by the overproduction of platelets associated with bone marrow megakaryocyte hyperplasia, and PMF with the deregulation of the megakaryocyte and granulocyte lineages [1,3,4].…”

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

“…However, a malignant clone, which can involve cells from various myeloid lineages, has been implicated in maintaining MPN inflammation as a key player [18,24,25]. Disruption of hematopoiesis and the establishment of an increased production of clonal myeloid cells gives rise to one of three classical MPN phenotypic outcomes: PV is characterized by an absolute increase in red cell mass, and increased number of leukocytes and platelets ("trilineage growth"), ET is characterized by overproduction of platelets and PMF with deregulation of the megakaryocyte and granulocyte lineages [3,45,52]. It is worth notifying that cells from all myeloid lineages in MPN neoplasms, including neutrophils, may belong to a malignant clone regardless of their total number in the circulation in a particular MPN phenotype.…”

Orthotopic Liver Transplantation for Budd-Chiari Syndrome: Observations from a 30-Year Liver Transplant Program

“…Nearly half of the patient population suffers from a myeloproliferative disorder in which a Janus kinase 2 (JAK2) mutation can be detected in peripheral granulocytes or hyperplastic megakaryocytes in the bone marrow [6]. These Philadelphia-chromosome Medicina 2021, 57, 821 2 of 12 negative myeloproliferative syndromes (MPS) include essential thrombocytosis (ET), polycythemia vera (PV), and myelofibrosis and require different diagnostics and treatments compared to other causes of BCS, including cytoreductive therapy [7]. Other common causes comprise antiphospholipid syndrome, factor V Leiden thrombophilia, protein C and protein S deficiency, as well as paroxysmal nocturnal hemoglobinuria (PNH).…”