Jung Yong Hong1, Ja-Young Seo2, Sun-Hee Kim3, Hyun Ae Jung4, Silvia Park4, Kihyun Kim4, Chul Won Jung4, Jin Seok Kim5, Joon Seong Park6, Hee-Jin Kim7, Jun Ho Jang8. 1. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea. 2. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Department of Laboratory Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea. 3. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 4. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 5. Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea. 6. Department of Oncology-Hematology, Ajou University School of Medicine, Suwon, Republic of Korea. 7. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea hee_jin.kim@samsung.com jh21.jang@samsung.com. 8. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea hee_jin.kim@samsung.com jh21.jang@samsung.com.
Abstract
BACKGROUND: Hypomethylating agents, such as azacitidine and decitabine, now constitute one of the mainstays of myelodysplastic syndrome (MDS) treatment. In recent years, novel recurrent mutations in multiple genes encoding RNA spliceosomal machinery (SRSF2, U2AF1, ZRSR2, SF3B1) were revealed. However, the clinical impact of these mutations on the outcomes of treatment of MDS patients with hypomethylating agents has not been described. PATIENTS AND METHODS: A total of 58 de novo MDS patients were included in the study who had received first-line decitabine treatment. Polymerase chain reaction (PCR) followed by direct sequencing analyses was performed for the spliceosomal machinery genes including SRSF2, U2AF1 and ZRSR2. RESULTS: In the present analysis of 58 Korean MDS patients, mutations in the splicing machinery genes SRSF2, U2AF1 and ZRSR2 were detected in 5 (8.6%), 10 (17.2%) and 6 (10.3%) patients, respectively, and the incidence of SRSF2 mutation was lower than those of previous series. The overall response rates (ORRs) including complete remission (CR), partial response (PR), and marrow CR (mCR) were 42.9% in the spliceosome wild-type (WT) group and 46.7% in the spliceosome-mutated group (p>0.999). The median OS was 22.0 months in the spliceosome-WT group and 15.9 months in the spliceosome-mutated group (p=0.267) CONCLUSION: This study firstly reports the impact of mutations of the spliceosomal machinery genes on the outcomes of decitabine treatment in MDS. The mutational status of the SRSF2, U2AF1 and ZRSR2 did not affect the response rate or survival in MDS patients who had received first-line decitabine treatment. Further studies are needed to confirm the prognostic relevance of spliceosome mutations to the clinical outcomes of treatment with hypomethylating agents. Copyright
BACKGROUND: Hypomethylating agents, such as azacitidine and decitabine, now constitute one of the mainstays of myelodysplastic syndrome (MDS) treatment. In recent years, novel recurrent mutations in multiple genes encoding RNA spliceosomal machinery (SRSF2, U2AF1, ZRSR2, SF3B1) were revealed. However, the clinical impact of these mutations on the outcomes of treatment of MDSpatients with hypomethylating agents has not been described. PATIENTS AND METHODS: A total of 58 de novo MDSpatients were included in the study who had received first-line decitabine treatment. Polymerase chain reaction (PCR) followed by direct sequencing analyses was performed for the spliceosomal machinery genes including SRSF2, U2AF1 and ZRSR2. RESULTS: In the present analysis of 58 Korean MDSpatients, mutations in the splicing machinery genes SRSF2, U2AF1 and ZRSR2 were detected in 5 (8.6%), 10 (17.2%) and 6 (10.3%) patients, respectively, and the incidence of SRSF2 mutation was lower than those of previous series. The overall response rates (ORRs) including complete remission (CR), partial response (PR), and marrow CR (mCR) were 42.9% in the spliceosome wild-type (WT) group and 46.7% in the spliceosome-mutated group (p>0.999). The median OS was 22.0 months in the spliceosome-WT group and 15.9 months in the spliceosome-mutated group (p=0.267) CONCLUSION: This study firstly reports the impact of mutations of the spliceosomal machinery genes on the outcomes of decitabine treatment in MDS. The mutational status of the SRSF2, U2AF1 and ZRSR2 did not affect the response rate or survival in MDSpatients who had received first-line decitabine treatment. Further studies are needed to confirm the prognostic relevance of spliceosome mutations to the clinical outcomes of treatment with hypomethylating agents. Copyright
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