In November 1981, a 77-yr-old woman consulted for myeloid metaplasia with fibrosis. A persistent hyperleucocytosis was treated with hydroxyurea from March, 1985 to March, 1989. At that time facial dyskinesia and polycythaemia developed. Investigations revealed a regression of myelofibrosis and a predominance of myeloid metaplasia in the liver. The mechanism of this event, rarely observed in myeloproliferative syndromes, is discussed in this new case.
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J Transl Med
January 2025
Department of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, Catania, Italy.
Background: Clonal myeloproliferation and fibrotic transformation of the bone marrow (BM) are the pathogenetic events most commonly occurring in myelofibrosis (MF). There is great evidence indicating that tumor microenvironment is characterized by high lactate levels, acting not only as an energetic source, but also as a signaling molecule.
Methods: To test the involvement of lactate in MF milieu transformation, we measured its levels in MF patients' sera, eventually finding a massive accumulation of this metabolite, which we showed to promote the expansion of immunosuppressive subsets.
Blood Cancer J
January 2025
School of Medicine, Faculty of Medicine and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Fedratinib is a predominantly JAK2 inhibitor that has shown efficacy in untreated and ruxolitinib-exposed patients with myelofibrosis (MF). Based on randomized clinical trial data, it is approved for use in patients with International Prognostic Scoring System (IPSS) or Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or high-risk disease and is distinguished from ruxolitinib in that it can be administered without dose reduction in patients with thrombocytopenia, to a platelet count above 50,000/µL. In these trials, fedratinib achieved significant spleen volume reduction in ~30-45% of patients and improvement in total symptom scores in 35-40% with good tolerability.
View Article and Find Full Text PDFBMC Cancer
January 2025
Centre for Medical Education, Queen's University Belfast, Belfast City Hospital, Lisburn Road, Belfast, UK.
Background: Myelofibrosis (MF) is a clonal haematopoietic disease, with median overall survival for patients with primary MF only 6.5 years. The most frequent gene mutation found in patients is JAK2, causing constitutive activation of the kinase and activation of downstream signalling.
View Article and Find Full Text PDFN Engl J Med
January 2025
From the Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Background: Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for myelofibrosis. Driver mutations are the pathophysiological hallmark of the disease, but the role of mutation clearance after transplantation is unclear.
Methods: We used highly sensitive polymerase-chain-reaction technology to analyze the dynamics of driver mutations in peripheral-blood samples from 324 patients with myelofibrosis (73% with mutations, 23% with mutations, and 4% with mutations) who were undergoing transplantation after reduced-intensity conditioning.
Cureus
December 2024
Hematology and Oncology, Olive View University of California Los Angeles (UCLA) Medical Center, Sylmar, USA.
Primary myelofibrosis (PMF) is an uncommon chronic myeloproliferative disorder that is commonly associated with Janus kinase 2 (JAK-2), calreticulin (CALR), or thrombopoietin receptor (MPL) mutations. Pre-fibrotic PMF (also known as pre-PMF or early PMF) is a subtype of PMF that is defined by a lower grade of fibrosis. In this report, we present a rare case of warm autoimmune hemolytic anemia (wAIHA) associated with pre-PMF.
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