Articles related to MYELOPROLIFERATIVE NEOPLASMS (MPNs)

The prognosis and therapy of grade 3 neuroendocrine neoplasms (NEN G3) depend on subgroup traits such as differentiation, proliferation rate, molecular profile, uptake on somatostatin receptor imaging, and primary site. Clinicians who treat this disease now have a better grasp of the prognosis and course of treatment for each entity thanks to the 2017 World Health Organization guidelines that split NEN G3 into neuroendocrine carcinomas (NEC) and NET G3. The distinction between NET G3 and NEC in upcoming trials and cancer registries will further improve prognosis and therapy options. Referral to a tertiary center is still of the utmost necessity at this time, considering the complexities of this disease. For the reasons described in this article, a referral also enables expert pathologic review, which is crucial. Further trials are undoubtedly necessary, considering the molecular heterogeneity of NEN G3.

JAK inhibitors have been the go-to treatment for people with myelofibrosis (MF). Despite successfully reducing MPN-related symptoms, currently approved JAK inhibitors are not known to significantly change the course of MF disease. Similar to essential thrombocythemia (ET) and polycythemia vera (PV), therapy in these conditions focus primarily on lowering the risk of cardiovascular and thromboembolic consequences; in individuals with reduced thrombosis risks, careful waiting is frequently employed. The creation of rationally tailored medicines, however, with the aim of not only managing illness problems but also potentially altering disease course, has resulted from a greater understanding of MPN biology.

A fully human IgG1 antibody that selectively binds to mutant CALR, INCA033989 demonstrated activity in cells from MPN patients and a mouse model of essential thrombocythemia. In the model, INCA033989 selectively decreased levels of mutant CALR-positive platelets, re-established normal megakaryopoiesis, and selectively targeted mutant CALR disease-initiating clones.

The use of thalidomide analogs, specifically lenalidomide, has been linked to an increased risk of TP53-mutated myeloid neoplasms. Furthermore, lenalidomide, but not pomalidomide, causes the expansion of preleukemic Trp53-mutant HSPCs via selective Ck1 degradation.

JAK inhibitors provide a relatively tolerable drug option for controlling symptoms, reducing splenomegaly, and improving quality of life, but often at the expense of worsening cytopenias and without halting disease progression or preventing leukemic transformation. In this article, the authors review FDA–approved JAK inhibitors as well as those in late-phase clinical trials, and provide a schema for choosing among the available options for patients with MF.

The International Consensus Classification (ICC) of myeloid neoplasms and acute leukemia was developed as a result of the recent advances in doctors’ understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials.