Clonal evolution process from essential thrombocythemia to acute myeloid leukemia in the original patient from whom the CALR -mutated Marimo cell line was established

We previously reported the Marimo cell line, which was established from the bone marrow cells of a patient with essential thrombocythemia (ET) at the last stage after transformation to acute myeloid leukemia (AML). This cell line is widely used for the biological analysis of ET because it harbors mutation. However, genetic processes during disease progression in the original patient were not analyzed. We sequentially analyzed the genetic status in the original patient samples during disease progression. The ET clone had already acquired and mutations, and and mutations affected the disease progression from ET to AML in this patient. Particularly, the variant allele frequency of the mutation increased along with the disease progression after transformation, and the -mutated clone selectively proliferated in vitro, resulting in the establishment of the Marimo cell line. Although and mutations co-existed, MPL was not expressed in Marimo cells or any clinical samples. Furthermore, mitogen-activated protein kinase (MAPK) but not the JAK2-STAT pathway was activated. These results collectively indicate that MAPK activation is mainly associated with the proliferation ability of Marimo cells.