Myeloproliferative Neoplasm

Among these, 11 were found to exert a protective effect against MPN, 5 phenotypes were associated with an elevated risk of MPN. This research highlights a significant association between various immune cell phenotypes and the risk of developing MPN, thereby advancing our understanding of the intricate interplay between immune cell traits and the progression of MPN.

Detected mutations were not found to be relevant to pathogenesis of T-LBL and MPN in previous reports and were considered variants of uncertain significance. Based on the WES results, ETV6::LYN fusion gene was considered the driver gene essential for the pathogenesis of MPN-TK with ETV6::LYN.

Our case study revealed that the pathogenic BRCA2 c.5946del germline variant can be associated with an unusual tumour spectrum, which may lead to a delayed diagnosis of a hereditary tumour predisposition. Thus, upfront genetic testing using large multigene panels or whole-genome sequencing in encouraged, especially in cases with a prominent family history.

P=N/A, N=50, Active, not recruiting, Institut National de la Santé Et de la Recherche Médicale, France | Recruiting --> Active, not recruiting

Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine. Median duration of CRc and ORR: 13.15 (range: 2.4-48.7) and 14.3 months (range: 2.4-48.7), respectively, and median overall survival: 13.8 months (95% confidence interval: 3.70-23.7). Olutasidenib demonstrated encouraging response rates with a manageable safety profile for patients with post-MPN mIDH1 AML.

FMNL1 plays a potential role in granulocyte differentiation and function, and its differential expression is linked to critical signaling pathways in leukemogenesis and inflammation. These findings highlight FMNL1's potential therapeutic implications in myeloid neoplasia, warranting further investigation.

P1/2, N=84, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | N=206 --> 84

P3, N=252, Terminated, Incyte Corporation | Active, not recruiting --> Terminated; The study was terminated due to futility.

Our report sheds light on the distinct clinical presentations of ET patients who develop AML, characterized by different TP53 mutations and varying therapeutic outcomes when treated with decitabine. However, further studies that include a larger quantity of samples are needed to elucidate the precise underlying molecular mechanisms involved in this process.

P1, N=50, Enrolling by invitation, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P3, N=240, Recruiting, Siriraj Hospital

P2, N=4, Active, not recruiting, Terrence J Bradley, MD | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

P=N/A, N=120, Recruiting, University Hospital, Bordeaux | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Although rare, myeloproliferative neoplasms can involve young patients and pose unique challenges for clinicians in diagnosis and therapy. The paper aims to review the biological markers of MPNs in pediatric populations-a particular group of patients that has been poorly studied due to the low frequency of MPN diagnosis.

Improved survival was observed with transplantation in groups DP2, DP7, and DP9. These findings highlight the role of genomic classifications in guiding personalized treatment strategies, ultimately enhancing the understanding and management of myeloid neoplasms.

These include new JAK inhibitors with greater specificity for JAK2, as well as "add-on" medications designed to enhance the effectiveness of ruxolitinib, in both patients who are new to the drug and in those who have shown suboptimal responses. Additionally, there is ongoing exploration of novel therapeutic targets. In this review, we will explore the immunotherapy approaches that are currently used in clinical practice for MPNs, as well as emerging strategies that are likely to change the treatment of these diseases in the coming years.

Knockdown of Laptm4b partially rescued Evi1-induced abnormal hematopoiesis in vivo. Thus, our study establishes a mouse model to investigate EVI1hi myeloid malignancies, demonstrating the significance of the EVI1-mediated KDM6B/H3K27me3/LAPTM4B signaling axis in their maintenance.

Both cancers were aggressively treated. The patient received autologous stem cell transplantation (ASCT) for multiple myeloma and tyrosine kinase inhibitor for chronic myeloid leukemia concurrently to achieve the complete response.

P1/2, N=179, Active, not recruiting, AbbVie | Trial completion date: Dec 2025 --> Dec 2026

Identification of germline predisposition is essential to understanding the pathogenesis of disease, impact on families, and opportunities for preventive care. Continued research is essential to further characterize the penetrance of these conditions, and how best to monitor, treat and optimize management for these families.

No abstract available

The consideration of such inherited traits is crucial for clinical management of patients, particularly with regards to indication for allogeneic hematopoietic cell transplant (allo-HCT) and donor selections. Herein, we describe the very instructive case of a 49-year-old woman diagnosed with JAK2 V617F-positive primary myelofibrosis (PMF) who was found to also carry a germline variant in the SH2B3 gene, detailing clinical management, donor selection process for allo-HCT purposes, and appropriate genetic counseling.

P1/2, N=150, Recruiting, Disc Medicine, Inc | N=56 --> 150 | Trial completion date: Oct 2024 --> Sep 2026 | Trial primary completion date: Oct 2024 --> Sep 2026

P3, N=38, Terminated, Celgene | Completed --> Terminated; Slow accrual.

We believe these observations warrant a comprehensive search for activated tyrosine kinases in myeloproliferative disorders and hematological malignancies, as there are likely additional unidentified genetic events with biological and therapeutic significance. Additional in vitro and in vivo studies are needed to determine the cause of the specificity of JAK2 V617F for myeloid and lymphoid diseases.

The prevalence of the JAK2 mutation among blood donors is similar to the general population's but slightly higher among repeat donors with elevated hematocrit. Further research is necessary to establish definitive upper hemoglobin limits for donor deferral.PROSPERO No.: CRD42023456878.

This case highlights the importance of considering myeloproliferative disorders in patients with atypical thrombotic and hemorrhagic events. It emphasizes the need for early diagnosis and appropriate treatment to optimize patient outcomes.

In ischemic cerebrovascular patients, the JAK2V617F mutation is associated with elevated markers of endothelial dysfunction and chronic inflammation. This underscores the role of inflammation in thrombosis driven by the JAK2V617F mutation.

P2, N=70, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Sep 2024 --> Jun 2025

The advantages of IFN therapy include a well-known safety profile, high rates of clinical and molecular responses, and a unique ability to deeply reduce the mutant allele burden of most of the driver mutations causing myeloproliferative neoplasms. Recent preliminary data from prospective studies suggest that molecular responses may be correlated with prolonged event-free survival, raising the hope that IFN therapy may ultimately alter the natural history of many diseases.

Pitfalls in diagnosis include subjectivity in assessing neutrophil dysplasia and distinguishing true neoplastic neutrophilia from reactive neutrophilias that may be superimposed upon or occur as a manifestation of the progression of other myeloid neoplasms. Accurate distinction between neutrophilic myeloid neoplasms is important, as it helps guide patient management and may disclose specific genetic lesions amenable to targeted therapy.

Additionally, WGS can identify unique SVs that may be missed by conventional methods and enables clinical benefits such as HLA typing for potential transplant (alloHCT) or diagnostic refinement by retroviral insertion (e.g. HTLV-1). These findings demonstrate the potential for integration of WGS into clinical practice to enhance personalized treatment strategies.

This paper describes a case of etv6-ascl6 fusion gene positive patient who was successively diagnosed as myelofibrosis, eosinophilic leukemia, basophilic leukemia and secondary acute myeloid leukemia. The clinical manifestations and disease evolution have its unique characteristics.

P2, N=29, Not yet recruiting, University of Alabama at Birmingham | Initiation date: Nov 2024 --> Jun 2025 | Trial primary completion date: Jan 2026 --> Dec 2026

P=N/A, N=200, Recruiting, University Hospital, Brest

P2, N=27, Recruiting, Xiamen Amoytop Biotech Co., Ltd. | Not yet recruiting --> Recruiting

In conclusion, our study provides valuable insights into the prevalence and characteristics of JAK2, CALR, and MPL mutations in BCR-ABL1 negative MPNs in the Moroccan population, highlighting the importance of genetic characterization to optimize the clinical management of these diseases.

We found that ASXL1, RUNX1, and KRAS can negatively impact these patients' survival with different impacts in different morphological diagnosis categories, suggesting a complex interaction between these genes. This study underscores the need for personalized approaches in the treatment of myeloid neoplasms.

P2, N=70, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: May 2025 --> Sep 2025 | Trial primary completion date: May 2025 --> Sep 2024

P2, N=25, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2025 --> Apr 2026 | Trial primary completion date: Dec 2024 --> Apr 2025

P1, N=231, Recruiting, Incyte Corporation | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Nov 2024 --> Dec 2025

In this issue of Blood, Reis et al1 identify a monoclonal antibody, INCA033989, that selectively targets mutant calreticulin (mutCALR) in myeloproliferative neoplasms (MPNs), inhibiting its oncogenic activity without affecting normal hematopoiesis.