TY - JOUR
T1 - Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia
AU - Yoshida, Nao
AU - Yagasaki, Hiroshi
AU - Xu, Yinyan
AU - Matsuda, Kazuyuki
AU - Yoshimi, Ayami
AU - Takahashi, Yoshiyuki
AU - Hama, Asahito
AU - Nishio, Nobuhiro
AU - Muramatsu, Hideki
AU - Watanabe, Nobuhiro
AU - Matsumoto, Kimikazu
AU - Kato, Koji
AU - Ueyama, Junichi
AU - Inada, Hiroko
AU - Goto, Hiroaki
AU - Yabe, Miharu
AU - Kudo, Kazuko
AU - Mimaya, Junichi
AU - Kikuchi, Akira
AU - Manabe, Atsushi
AU - Koike, Kenichi
AU - Kojima, Seiji
PY - 2009/3
Y1 - 2009/3
N2 - Mutations in RAS, neurofibromatosis type 1 (NF1), and PTPN11, constituents of the granulocyte-macrophage colony-stimulating factor signaling pathway, have been recognized in patients with juvenile myelomonocytic leukemia (JMML). We assessed 71 children with JMML for NRAS, KRAS, and PTPN11 mutations and evaluated their clinical significance. Of the 71 patients, three had been clinically diagnosed with neurofibromatosis type 1, and PTPN11 and NRAS/KRAS mutations were found in 32 (45%) and 13 (18%) patients, respectively. No simultaneous aberrations were found. Compared with patients with RAS mutation or without any aberrations, patients with PTPN11 mutation were significantly older at diagnosis and had higher fetal Hb levels, both of which have been recognized as poor prognostic factors. As was expected, overall survival was lower for patients with the PTPN11 mutation than for those without (25 versus 64%; p = 0.0029). In an analysis of 48 patients who received hematopoietic stem cell transplantation, PTPN11 mutations were also associated with poor prognosis for survival. Mutation in PTPN11 was the only unfavorable factor for relapse after hematopoietic stem cell transplantation (p = 0.001). All patients who died after relapse had PTPN11 mutation. These results suggest that JMML with PTPN11 mutation might be a distinct subgroup with specific clinical characteristics and poor outcome.
AB - Mutations in RAS, neurofibromatosis type 1 (NF1), and PTPN11, constituents of the granulocyte-macrophage colony-stimulating factor signaling pathway, have been recognized in patients with juvenile myelomonocytic leukemia (JMML). We assessed 71 children with JMML for NRAS, KRAS, and PTPN11 mutations and evaluated their clinical significance. Of the 71 patients, three had been clinically diagnosed with neurofibromatosis type 1, and PTPN11 and NRAS/KRAS mutations were found in 32 (45%) and 13 (18%) patients, respectively. No simultaneous aberrations were found. Compared with patients with RAS mutation or without any aberrations, patients with PTPN11 mutation were significantly older at diagnosis and had higher fetal Hb levels, both of which have been recognized as poor prognostic factors. As was expected, overall survival was lower for patients with the PTPN11 mutation than for those without (25 versus 64%; p = 0.0029). In an analysis of 48 patients who received hematopoietic stem cell transplantation, PTPN11 mutations were also associated with poor prognosis for survival. Mutation in PTPN11 was the only unfavorable factor for relapse after hematopoietic stem cell transplantation (p = 0.001). All patients who died after relapse had PTPN11 mutation. These results suggest that JMML with PTPN11 mutation might be a distinct subgroup with specific clinical characteristics and poor outcome.
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U2 - 10.1203/PDR.0b013e3181961d2a
DO - 10.1203/PDR.0b013e3181961d2a
M3 - Article
C2 - 19047918
AN - SCOPUS:61949288688
SN - 0031-3998
VL - 65
SP - 334
EP - 340
JO - Pediatric Research
JF - Pediatric Research
IS - 3
ER -