The relationship between fibrosis and the microenviroment and additional mutations in BCR-ABL negative myeloproliferative neoplasms

Myeloproliferative neoplasms are clonal stem cell disorders characterized by proliferation in the myeloid lineage. Although bone marrow biopsy remains the gold standard for diagnosis and molecular mutations provide supportive evidence, the cellular targets underlying bone marrow fibrosis remain unclear. In our study, we compared age, sex, bone marrow microenvironment, megakaryocyte morphology, fibrosis grade, mutational status, and prognostic data in 44 cases diagnosed with Essential Thrombocythemia, Polycythemia Vera, and Primary Myelofibrosis. The microenvironment was evaluated using immunohistochemical staining with antibodies against Glioma-Associated Oncogene 1, Platelet Factor 4, and Stromal Cell-Derived Factor 1. According to the study results, the presence of cloud-like nuclei in megakaryocytes showed a significant association with grade 2 fibrosis and Glioma-Associated Oncogene 1 positivity. In the immunohistochemical evaluation of the microenvironment, there was a statistically significant correlation between the percentage of Glioma-Associated Oncogene 1 staining and the degree of fibrosis. Glioma-Associated Oncogene 1 positivity was also significantly associated with higher blast percentage and the presence of Janus Kinase 2 mutations. Platelet Factor 4 staining showed a meaningful relationship with fibrosis grade and the presence of mutations in Calreticulin , Tet Methylcytosine Dioxygenase 2, U2 Small Nuclear Auxiliary Factor 1, and Enhancer of Zeste Homolog 2. Regarding additional mutations, Additional Sex Combs Like 1 and Enhancer of Zeste Homolog 2 mutation in particular demonstrated a statistically significant association with mortality. Additional Tumor Protein p53 mutations were found to be associated with increased blast percentage. In conclusion, our study aimed to elucidate the mechanisms underlying bone marrow fibrosis, identify molecular targets, and contribute to the development of new therapeutic approaches. Alongside bone marrow transplantation a high-risk procedure associated with high mortality in the treatment of myelofibrosis Glioma-Associated Oncogene 1 antagonists may represent a promising therapeutic option for the treatment of fibrosis.