Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia.
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.
Matsuda
Kazuyuki
K
Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Japan.
Sakashita
Kazuo
K
Taira
Chiaki
C
Tanaka-Yanagisawa
Miyuki
M
Yanagisawa
Ryu
R
Shiohara
Masaaki
M
Kanegane
Hirokazu
H
Hasegawa
Daiichiro
D
Kawasaki
Keiichiro
K
Endo
Mikiya
M
Yajima
Shuhei
S
Sasaki
Shinya
S
Kato
Keisuke
K
Koike
Kazutoshi
K
Kikuchi
Akira
A
Ogawa
Atsushi
A
Watanabe
Akihiro
A
Sotomatsu
Manabu
M
Nonoyama
Shigeaki
S
Koike
Kenichi
K
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*
D004273:DNA, Neoplasm; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11