title: Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia.
abstract: To evaluate minimal residual disease (MRD) after chemotherapy and haematopoietic stem cell transplantation in juvenile myelomonocytic leukaemia (JMML), a locked nucleic acid-allele specific quantitative polymerase chain reaction (LNA-AS-qPCR) was developed for 13 patients (four types of PTPN11 mutation and four types of RAS mutation). The post-transplant MRD detected by LNA-AS-qPCR analysis was well correlated with chimerism assessed by short tandem repeat PCR analysis. Non-intensive chemotherapy exerted no substantial reduction of the tumour burden in three patients. There was no significant difference in the quantity of RAS mutant DNA after spontaneous haematological improvement in 4 patients with NRAS or KRAS 34G > A during a 2- to 5-year follow-up. PTPN11, NRAS, or KRAS mutant DNA was detected from Guthrie card dried blood in five of seven patients (who were aged <2 years at diagnosis) at a level of 1.0-6.5 x 10(-1) of the values at diagnosis. Accordingly, these five patients might have already reached a subclinical status at birth. Considering the negative correlation between mutant DNA level in neonatal blood spots and age at diagnosis, JMML patients with a larger tumour burden at birth appeared to show earlier onset.
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsuda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakashita
authors.forename: Chiaki
authors.initials: C
authors.lastname: Taira
authors.forename: Miyuki
authors.initials: M
authors.lastname: Tanaka-Yanagisawa
authors.forename: Ryu
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiohara
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Hasegawa
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Mikiya
authors.initials: M
authors.lastname: Endo
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yajima
authors.forename: Shinya
authors.initials: S
authors.lastname: Sasaki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kato
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Koike
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Watanabe
authors.forename: Manabu
authors.initials: M
authors.lastname: Sotomatsu
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
mesh_terms: D000367:Age Factors; D004273:DNA, Neoplasm / Q000235:genetics; D005500:Follow-Up Studies; D011905:Genes, ras; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007231:Infant, Newborn; D054429:Leukemia, Myelomonocytic, Juvenile / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11