Premium
Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia
Author(s) -
Matsuda Kazuyuki,
Sakashita Kazuo,
Taira Chiaki,
TanakaYanagisawa Miyuki,
Yanagisawa Ryu,
Shiohara Masaaki,
Kanegane Hirokazu,
Hasegawa Daiichiro,
Kawasaki Keiichiro,
Endo Mikiya,
Yajima Shuhei,
Sasaki Shinya,
Kato Keisuke,
Koike Kazutoshi,
Kikuchi Akira,
Ogawa Atsushi,
Watanabe Akihiro,
Sotomatsu Manabu,
oyama Shigeaki,
Koike Kenichi
Publication year - 2010
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07968.x
Subject(s) - neuroblastoma ras viral oncogene homolog , kras , ptpn11 , juvenile myelomonocytic leukemia , medicine , leukocytosis , mutation , transplantation , biology , polymerase chain reaction , immunology , oncology , gastroenterology , stem cell , haematopoiesis , cancer , genetics , colorectal cancer , gene
Summary 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 × 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.