Association of the composition of the bone marrow tumor microenvironment in BCR::ABL1-negative myeloproliferative neoplasms with IFN-γ signaling and driver mutations https://www.nature.com/articles/s41375-025-02706-3 Plain English Summary: The study investigates a type of blood cancer known as BCR:ABL1-negative myeloproliferative neoplasms (MPN), which includes conditions like essential thrombocythemia and polycythemia vera. These diseases are characterized by an overproduction of blood cells and are often linked to mutations in the JAK2 gene. Key Findings: JAK2 Mutations and Immune Response: The research found that patients with JAK2 mutations have an activated signaling pathway involving interferon-gamma (IFN-γ), which is important for immune responses. This activation occurs even without the presence of IFN-γ in the surrounding environment. Bone Marrow Environment: The study analyzed bone marrow samples from 265 MPN patients and compared them to healthy controls. It showed that the bone marrow of MPN patients had a higher expression of genes related to IFN-γ signaling, particularly in immune cells like lymphocytes and monocytes. Tumor-Infiltrating Lymphocytes (TILs): A significant finding was that higher levels of tumor-infiltrating lymphocytes were associated with better patient outcomes. This suggests that a robust immune response may help control the disease. Prognostic Clusters: The researchers identified two clusters of patients based on their immune profiles. One cluster, characterized by higher immune activity and TILs, was linked to better survival rates. Implications for Treatment: Understanding how JAK2 mutations influence immune signaling could lead to new treatment strategies for MPN, potentially improving patient outcomes by enhancing the immune response against the cancer. In summary, this study highlights the complex relationship between genetic mutations in MPN, immune signaling pathways, and patient prognosis, suggesting that enhancing immune responses could be a key strategy in treating these blood cancers. (fb)

Study Identifies Potential Genetic Drivers, Targeted Treatments for AF in MPN (fb)