| Affiliation: | 1. Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto;2. Department of Paediatrics, Shinshu University School of Medicine, Matsumoto;3. Department of Paediatrics, Graduate School of Medicine, University of Toyama, Toyama;4. Department of Haematology and Oncology, Kobe Children’s Hospital, Kobe;5. Department of Paediatrics, School of Medicine, Iwate Medical University, Morioka;6. Hamamatsu Medical Centre, Hamamatsu;7. Department of Paediatrics, Hirosaki University School of Medicine, Hirosaki;8. Department of Paediatrics, Ibaraki Children’s Hospital, Mito;9. Division of Haematology/Oncology, Saitama Children’s Medical Centre, Saitama;10. Department of Paediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo;11. Department of Paediatrics, Niigata Cancer Centre Hospital, Niigata;12. Division of Haematology‐Oncology, Gunma Children’s Medical Centre, Shibukawa;13. Department of Medical Informatics, National Defence Medical College, Tokorozawa, Japan |
| 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 × 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. |
