Characteristics of RAS pathway mutations in juvenile myelomonocytic leukaemia: a single‐institution study from Korea. (30th September 2021)

• Record Type: Journal Article
• Authors: Kim, Hoon Seok; Lee, Jae Wook; Kang, Dain; Yu, Haein; Kim, Yeojae; Kang, Hyunhye; Lee, Jong‐Mi; Ahn, Ari; Cho, Bin; Kim, Seongkoo; Chung, Nack‐Gyun; Kim, Yonggoo; Kim, Myungshin
• Is Part Of: British journal of haematology. Volume 195:Number 5(2021)
• Page Start: 748
• Page End: 756
• Publication Date: 2021-09-30
• Subjects: juvenile myelomonocytic leukaemia -- genetic characteristics -- RAS pathway -- secondary mutations -- haematopoietic stem cell transplantation; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.17861
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: Juvenile myelomonocytic leukaemia (JMML), a rare clonal haematopoietic disorder of childhood, is characterised as a myelodysplastic/myeloproliferative neoplasm. Despite ground‐breaking genetic discoveries, JMML remains difficult to diagnose given its diverse clinical features and disease course. A total of 24 patients with JMML were diagnosed and treated at a single institution, and their genetic profiles and association with clinical and laboratory characteristics were analysed. In all, 22 of the patients received allogeneic haematopoietic stem cell transplantation after myeloablative conditioning, mostly from a haploidentical family donor. RAS pathway mutations were identified in 88% of patients: PTPN11 [nine (38%)], NRAS [nine (38%)], KRAS [two (8%)], NF1 [five (21%)] and CBL [one (4%)]. Secondary mutations were found in 25% of patients: SETBP1, JAK3, ASXL1, GATA2, KIT, KDM6A, and BCOR . Six patients showed cytogenetic abnormalities, including three with monosomy 7. The estimated 5‐year event‐free survival (EFS) and overall survival (± standard error) of the entire cohort were 58·9 (10·9)% and 73·5 (10·8)% respectively. NRAS (+) patients had a higher 5‐year EFS than NRAS (−) patients [72·9 (16·5)% vs. 52·5 (13·1)%, P = 0·127]. NRAS (+) patients had a better 5‐year EFS than PTPN11 (+) patients [41·7 (17·3)%, P = 0·071]. Our study revealed the genetic characteristics of Korean JMML patients with RAS pathway and secondary mutations.