TY - JOUR
T1 - Characteristics of RAS pathway mutations in juvenile myelomonocytic leukaemia
T2 - a single-institution study from Korea
AU - Kim, Hoon Seok
AU - Lee, Jae Wook
AU - Kang, Dain
AU - Yu, Haein
AU - Kim, Yeojae
AU - Kang, Hyunhye
AU - Lee, Jong Mi
AU - Ahn, Ari
AU - Cho, Bin
AU - Kim, Seongkoo
AU - Chung, Nack Gyun
AU - Kim, Yonggoo
AU - Kim, Myungshin
N1 - Publisher Copyright:
© 2021 British Society for Haematology and John Wiley & Sons Ltd.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - RAS pathway
KW - genetic characteristics
KW - haematopoietic stem cell transplantation
KW - juvenile myelomonocytic leukaemia
KW - secondary mutations
UR - https://www.scopus.com/pages/publications/85115942786
U2 - 10.1111/bjh.17861
DO - 10.1111/bjh.17861
M3 - Article
C2 - 34590720
AN - SCOPUS:85115942786
SN - 0007-1048
VL - 195
SP - 748
EP - 756
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 5
ER -