Myeloproliferative Neoplasm

We showed the efficacy of daratumumab in combination with targeted therapies for the treatment of pulmonary MM.

Moreover, this increase disappears in CML patients after treatment with tyrosine kinase inhibitors when the curative effect was satisfactory. We conclude that an increase in the proportion of CD56briCD38+ neutrophil subsets exceeding 2.0 % of total neutrophils serves as a highly sensitive and specific flow cytometry marker, enabling rapid and accurate identification of CML.

P2, N=54, Recruiting, Icahn School of Medicine at Mount Sinai | Not yet recruiting --> Recruiting

Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea. To decrease the risk of thrombosis, all patients with PV should be treated with aspirin and therapeutic phlebotomy to maintain a hematocrit of less than 45%. Cytoreductive therapies, such as hydroxyurea or interferon, are recommended for patients at high risk of thrombosis.

P2, N=47, Completed, Incyte Corporation | Active, not recruiting --> Completed

These novel time-dependent transfusion burden analyses demonstrate that momelotinib is associated with anemia-related benefits in most patients and greater transfusion burden reduction versus comparators.

Individualized treatment decisions should consider patient-specific factors, emphasizing collaborative efforts between specialists to optimize DOAC therapy in patients with MPNs. Comparable efficacy and safety between DOACs and VKAs were observed in MPN patients.

This study demonstrates that oncoReveal MLH1 and MGMT Methylation Panel performed very well against comparator methods. The performance characteristics and workflow benefits are suitable for clinical testing.

Determination of IDH1-2 mutation status is important for a variety of malignancies for diagnostics, classification, prognosis, and therapy selection. The Idylla system is easy to use and requires little training; therefore, it is the ideal assay to implement in a variety of labs. Overall, the Idylla platform provides quick, dependable, and easy-to-use technology for performing this analysis.

This project highlights the application of creative and robust methods of molecular diagnostics for LMICs, allowing for the treatment and monitoring of patients with previously limited access to assays and medications widely available in Western industrialized countries.

The MPN NGS panel demonstrated excellent clinical utility, as 96% (26/27) of significant JAK2/CALR/MPL variants were identified in our cohort. The detection rate of predominately JAK2 variants with rare CALR and MPL variants is in line with the current literature. Based on the findings of patients that underwent the pan-heme panel, potential expansion of coverage regions in JAK2 to include additional exons (such as exon 16) could further improve the detection rate.

This intra-laboratory study demonstrates that the oncoReveal Essential MPN Panel performed very well against comparator methods. The performance characteristics, workflow benefits, and TAT saving are suitable for clinical testing of MPN patient population to allow accurate clinical assessment.

P2, N=2, Terminated, Weill Medical College of Cornell University | N=37 --> 2 | Trial completion date: Sep 2025 --> Jul 2024 | Recruiting --> Terminated; Low accrual

P3, N=300, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University of

P2, N=101, Active, not recruiting, Gruppo Italiano Malattie EMatologiche dell'Adulto | Recruiting --> Active, not recruiting | Trial completion date: May 2024 --> Apr 2026 | Trial primary completion date: May 2024 --> Oct 2024

P3, N=67, Recruiting, PharmaEssentia Japan K.K. | Trial completion date: Oct 2024 --> Jun 2026 | Trial primary completion date: Oct 2024 --> Jun 2026

P2, N=25, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting

DTA mutations detected with a clinically used NGS panel in patients with MPN are associated with increased risk of bleeding complications, as well as increased thrombotic risk in a subgroup of patients. These findings support the incorporation of molecular panel analyses in thrombosis and bleeding risk assessment in MPN, and merit further investigation.

P4, N=70, Not yet recruiting, PharmaEssentia | N=110 --> 70 | Trial completion date: Feb 2027 --> Jun 2026 | Initiation date: Jul 2024 --> Jan 2025

P2, N=71, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> Nov 2023

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

P=N/A, N=170, Completed, University Hospital, Brest | Unknown status --> Completed | N=125 --> 170

The incidence rate of PH in Ph- MPNs patients is high, and its risk factors are diverse. The OS rate of Ph- MPNs patients with PH is low. Therefore, we should be highly alert to the occurrence of PH in Ph- MPNs patients clinically.

Down-regulation of PAK1 can significantly inhibit the growth of 6133/MPL cells, promote the formation of polyploid DNA, induce 6133/MPL cell apoptosis, and prolong the survival time of 6133/MPL mice.

Both TAM and ML-DS are characterized by proliferation of megakaryoblasts carrying a mutation in the GATA1 gene. Here, we report four cases with educational significance, highlighting typical diagnostic features that facilitate the differentiation between these two conditions, thereby assisting clinicians and medical laboratory professionals in effectively managing and monitoring these patients.

The application of FLAER in PNH-positive and PNH-negative reactive or malignant BM aspirates identified normally expected non-PNH FLAER-dim CD34-/CD117+/HLA-DR+/CD33+ myeloid precursors in all samples. A specific FLAER-associated maturation pattern was observed, which is proposed for further study within MRD and diagnostic protocols.

Here, we provide an overview of MPN disease evolution associated events incidence and conduct an exhaustive comparative review of the scoring systems currently available for each risk. Finally, we propose an algorithm for the use of these scores in clinical practice in each MPN subtype.

MPNs with JAK2 mutations are associated with SCAD in addition to usual atherosclerosis. This association needs further research.

P2, N=7, Active, not recruiting, City of Hope Medical Center | N=12 --> 7

P1/2, N=52, Recruiting, Uma Borate | Not yet recruiting --> Recruiting

In this study, through a patient-sample driven transcriptomic and epigenetic description of the MF microenvironment landscape and cell-based analyses, we identify HOXB7 overexpression and more precisely a novel TGFβ-Wnt-HOXB7 pathway as associated to a pro-fibrotic and pro-osteoblastic biased differentiation of mesenchymal stromal cells (MSCs). Using gene-based and chemical inhibition of this pathway we reverse the abnormal phenotype of MSCs from myelofibrosis patients, providing the MPN field with a potential novel target to prevent and manage evolution to MF.

Patients may have have underlying TKD mutations at prestation or may develop during course of disease. In case of TKI resistance, testing for specific mutations must be done and appropriate TKI sensitive to underlying mutation is to be used which translates into improved OS.

P2, N=42, Completed, French Innovative Leukemia Organisation | Recruiting --> Completed | Trial completion date: Sep 2025 --> Dec 2023

P1/2, N=260, Recruiting, BeiGene | Phase classification: P1b/2 --> P1/2 | Trial completion date: Aug 2025 --> Feb 2028 | Trial primary completion date: Dec 2023 --> Feb 2028

More recently, certain medications were implicated, including TNF-alpha inhibitors, rituximab, and IL-17A inhibitors, such as secukinumab, where the development of PG is held to represent a cutaneous immune adverse effect...One patient received the anti-calcitonin gene-related peptide targeted therapy, erenumab, for migraine prophylaxis...We documented a microenvironment enriched in IL-17A, emphasizing that the blockade impacts the functionality of the receptor as opposed to a quantitative reduction in IL-17A production by T cells. Qualitative functional IL-17A blockade could result in a paradoxical increase in IL-23, a pro-inflammatory cytokine that may contribute to the influx of neutrophils pathogenetically implicated in PG.

The results showed lower expression of HOTAIR and PTGS2 in CML patients. The HOTAIR expression is inversely associated with BCR::ABL1 expression in imatinib-treated CML patients, and to PTGS2 showing that CML patients with high BCR::ABL1 expression showed reduced PTGS2 expression.

Finally, we present the interferon alpha (IFNα) therapy as a potential early disease-modifying drug after reporting its good hematological and molecular efficacies in ET, PV and early MF in clinical trials as well as its mechanism of action in pre-clinical studies. As a result, we may expect that, in the future, MPN patients will be diagnosed very early during the course of disease and that new selective therapies under development, such as IFNα, JAK2V617F inhibitors and CALRmut monoclonal antibodies, would be able to intercept the mutated clones.

P1/2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=36 --> 0 | Initiation date: Jul 2024 --> Jan 2025 | Not yet recruiting --> Withdrawn

P2, N=91, Active, not recruiting, PharmaEssentia | Recruiting --> Active, not recruiting | N=64 --> 91 | Trial completion date: Dec 2026 --> Mar 2027 | Trial primary completion date: Jul 2024 --> Mar 2027

Current therapeutic strategies include JAK inhibitors like Ruxolitinib, which target the JAK-STAT pathway, alongside supportive treatments such as blood transfusions, erythropoiesis-stimulating agents and developing combinatorial approaches...Recently approved JAK inhibitors, including Fedratinib, Pacritinib, and Momelotinib, have expanded the therapeutic landscape...These technologies elucidate the role of the spleen in MF, highlighting its transformation into a site of abnormal hematopoietic activity, fibrotic changes, and immune cell infiltration, functioning as a "tumor surrogate." By profiling diverse cell populations and molecular alterations within the BM and spleen, SRT facilitates a deeper understanding of MF pathophysiology, helping identify novel therapeutic targets and biomarkers. Ultimately, integrating spatial transcriptomics into MF research promises to enhance diagnostic precision and therapeutic innovation, addressing the multifaceted challenges of this disease.

In conclusion, we show a JAK2-dependent down regulation of SHP-1 in MPN patients' cells which is related to their resistance to the antiproliferative effect of TGF-β. This may participate in the clonal selection of cancer cells in MPNs.

Antiplatelet therapy was started with acetylsalicylic acid 100 mg and clopidogrel 75 mg once a day. With the recommendation of hematology, cytoreductive treatment, hydroxyurea 1000 mg twice a day, was started. The patient's complaints were resolved at the end of the second day, and the patient with minimal ataxia was discharged with recommendations. Patients with ET should be aware of ischemic cerebrovascular disease and consider antiplatelet and cytoreductive treatment options.