Impact of Cooperating Myeloid Gene Mutations on Disease Progression and Survival in Japanese MPN Patients: A Multicenter Study

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.1805-1805
• Main Authors: Ogawa, Saki, Shide, Kotaro, Takeuchi, Masami, Matsue, Kosei, Kameda, Takuro, Yasumi, Masato, Karasuno, Takahiro, Shimomura, Taizo, Suzushima, Hitoshi, Yamashita, Kiyoshi, Kawano, Noriaki, Imataki, Osamu, Kadowaki, Norimitsu, Yonezawa, Akihito, Otsuka, Eiichi, Saburi, Yoshio, Tahira, Yuki, Kamiunten, Ayako, Akizuki, Keiichi, Karasawa, Masayoshi, Ikeda, Ryoma, Matsumoto, Kengo, Kuroki, Ayuka, Nagamine, Koshiro, Kubuki, Yoko, Shimoda, Kazuya
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-208908

In addition to driver mutations such as JAK2, CALR, and MPL, some patients with Polycythemia vera (PV), Essential thrombocythemia (ET), and Primary myelofibrosis (PMF) also have mutations common to other myeloid tumors. We conducted this study from 2018 to clarify the impact of such cooperating myeloid gene mutations on survival in real-world clinical settings. We included 622 MPN patients (PV 180, ET 360, PMF 82) from 8 hospitals who were examined for driver mutations for diagnosis and diagnosis confirmation at the University of Miyazaki from March 2007 to March 2023. 69.1% of all DNA samples were collected within 1 year from diagnosis. We investigated gain-of-function hotspot mutations in six genes (IDH1, IDH2, ASXL1, U2AF1, SF3B1, U2AF1) using Sanger sequencing. Loss-of-function mutations without hotspots (e.g., EZH2, TP53, ZRSR2, RUNX1) were not investigated. We retrospectively investigated overall survival and disease progression (progression to myelofibrosis or leukemia in PV and ET, and progression to leukemia in PMF). The median observation period was 5.1, 5.9, and 3.1 years for PV, ET, and PMF, respectively. One or more cooperating mutations were found in 9.4%, 11.7%, and 43.9% of PV, ET, and PMF cases, respectively, with ASXL1 being the most common mutation found in 5.4%, 7.3%, and 26.8% of cases. The incidence of disease progression in PV and ET patients was 0.066 and 0.098 at 10 years, respectively. Patients with cooperating mutations had a higher rate of progression than patients without these mutations (PV: 0.348 vs 0.029, p=0.0088; ET: 0.388 vs 0.060, p