A Novel Cell Line, Tnet-2, Derived From "Triple-Negative" Essential Thrombocythemia

【Introduction】 Myeloproliferative neoplasm (MPN) is a heterogeneous group of disorders, including Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). It is known that mutations of JAK2, CALR, or MPL gene are causative alternations of MPNs. However, 10-15% of MPNs have no mutations in any of these three genes, so-called “triple negative” (TN) MPN. It remains unclear that what genetic alternations cause TN-MPN. Cell lines derived from clonal hematopoietic disorders are useful tools to characterize diseases as well as to identify effective reagents for such diseases. To our knowledge, there is no cell line derived from TN-MPN although there are several lines with JAK2 V617F or CALR mutation. We have encountered an aggressive ET case with TN phenotype. Three years after initial diagnosis, blastic transformation occurred in this patient. Both conventional chemotherapy and allogeneic transplantation failed to cure the patient. After relapse, various therapies including ruxolitinib (JAK inhibitor) failed to control the disease. We have successfully established a cell line from the leukemic cells of this patient. We have also characterized the cell line by whole genome sequencing (WGS), RNA sequencing (RNA-Seq), as well as in vitro assays.