Causal relationship between 731 immune cells and the risk of myeloproliferative neoplasms: A 2-sample bidirectional Mendelian randomization study.

Myeloproliferative neoplasms (MPN) are chronic hematological disorders marked by the abnormal proliferation of bone marrow cells. The most commonly encountered forms are polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET). These disorders are generally associated with increases in blood components, which can lead to conditions like splenomegaly, thrombosis, bleeding tendencies, and a heightened risk of progressing to acute leukemia.

Evaluation of gecacitinib vs hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis: final analysis results from a randomized phase 3 study.

To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24.

rearranged acute myeloid leukemia transformed from V617F mutated primary myelofibrosis.

Acute myeloid leukemia (AML) with fusion is rare with largely unknown clinicopathological features and genomic characterization. We present one such case of AML transformed from V617F mutated primary myelofibrosis and review the literature on this topic. The immunophenotype and the landscape of cooperative gene alterations in AML with resemble those of AML with , including expression of CD19, cooperative gene alterations in signaling pathway (), epigenetic/chromatin and cell cycle regulation (, , and ), and additional chromosomal abnormalities (trisomies 8 and 15).

Biological Markers of Myeloproliferative Neoplasms in Children, Adolescents and Young Adults.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic cancers characterized by hyperproliferation of the myeloid lineages. These clonal marrow disorders are extremely rare in pediatric patients. MPN is reported to occur 100 times more frequently in adults, and thus research is primarily focused on this patient group.

Anemia in Myelofibrosis: A Focus on Proactive Management and the Role of Momelotinib.

Anemia is a common and progressive clinical manifestation of myelofibrosis that may occur as part of the disease pathogenesis as well as due to the myelosuppressive effects of some treatments, with a substantial impact on quality of life, prognosis, and healthcare resource utilization. Despite these burdens, anemia management has traditionally been a secondary priority to spleen and symptom control, due in part to the limitations of available therapeutic approaches. With the initial regulatory approvals of momelotinib, a Janus kinase 1 (JAK1), JAK2, and activin A receptor type 1 inhibitor that provides anemia-related benefits in addition to addressing splenomegaly and symptoms, re-evaluation of anemia as an early and prominent treatment consideration is warranted.

Case report: Successful use of ruxolitinib to treat interstitial pneumonia as an unusual primary presentation in primary myelofibrosis-two birds with one stone.

Background: Interstitial lung disease (ILD) is a rare clinical presentation of primary myelofibrosis (PMF).

Case Presentation: We report a case of ILD as the main manifestation on admission. A 58-year-old man was diagnosed with PMF owing to worsening anemia following treatment failure for conventional interstitial pneumonia.

Prognostic significance of LOXL2 enzyme activity in primary myelofibrosis.

Primary myelofibrosis (PMF) is characterized by bone marrow fibrosis, but the underlying molecular mechanisms remain incompletely understood. Here, we investigated the role of lysyl oxidase-like 2 (LOXL2), an enzyme involved in extracellular matrix remodeling, in PMF pathogenesis. Analysis of bone marrow cells from PMF patients revealed significantly elevated LOXL2 mRNA expression compared to healthy controls, which was further validated using 2 independent Gene Expression Omnibus datasets (GSE26049 and GSE12234).

Pegylated interferon: the who, why, and how.

Interferon alpha (IFN-α) is a fascinating molecule with many biological properties yet to be fully understood. Among these properties, several have demonstrated usefulness for targeting malignant cells, including hematopoietic cells from patients with myeloproliferative neoplasms. Indeed, IFN-α has been used for decades across all myeloproliferative neoplasms, but only recently a new form, ropegIFN-α2b, was approved to treat patients with polycythemia vera.

Role of molecular alterations in transplantation decisions for patients with primary myelofibrosis.

The aim of our study was to analyze the potential survival benefit associated with HSCT according to clinico-biological scores which incorporate molecular data (MIPSS70 and MIPSS70+V2) to facilitate decision-making in this context. One transplant (n=241) and one non-transplant cohorts (n=239) were used to test the hypothesis that PMF patients with higher risk molecular score benefit from HSCT. A weighted propensity score was applied to balance confounding factors with the transplanted cohort as reference.

Outcomes of patients with acute myeloid leukemia and bone marrow fibrosis.

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML.

Myeloproliferative Neoplasm-like Mutations of Calreticulin Induce Phenotypes Associated with Calreticulin Dysfunction in .

In previous research, we created a model with homozygous mutations in calreticulin similar to those found in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), two myeloproliferative neoplasms (MPNs). This model, lacking JAK orthologs, enabled us to examine the transcriptomic effects caused by mutant calreticulin without the influence of JAK/STAT activation, the primary pathogenic mechanism associated with calreticulin mutations known to date. Most of the gene expression changes observed seemed to be due to a partial loss of protein function, with the alteration of the extracellular matrix being particularly notable.