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- Title
Clonal evolution process from essential thrombocythemia to acute myeloid leukemia in the original patient from whom the CALR-mutated Marimo cell line was established.
- Authors
Yoko Ushijima; Yuichi Ishikawa; Takahiro Nishiyama; Naomi Kawashima; Takashi Kanamori; Masashi Sanada; Hitoshi Kiyoi
- Abstract
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 CALR 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 CALR and MPL mutations, and TP53 and NRAS mutations affected the disease progression from ET to AML in this patient. Particularly, the variant allele frequency of the NRAS mutation increased along with the disease progression after transformation, and the NRAS-mutated clone selectively proliferated in vitro, resulting in the establishment of the Marimo cell line. Although CALR and MPL 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.
- Subjects
ACUTE myeloid leukemia; CELL lines; MITOGEN-activated protein kinases; THROMBOCYTOSIS; BONE marrow cells; PRELEUKEMIA
- Publication
Nagoya Journal of Medical Science, 2024, Vol 86, Issue 2, p326
- ISSN
0027-7622
- Publication type
Article
- DOI
10.18999/nagjms.86.2.326