Genetic analysis of TP53 in childhood myelodysplastic syndrome and juvenile myelomonocytic leukemia.

Among 9 children with myelodysplastic syndrome (MDS) and 18 children with juvenile myelomonocytic leukemia, one MDS patient with der(5;17)(p10;q10) exhibited deletion of the TP53 gene in one allele and mutation (410 T>A) in the other allele in myeloid and erythroid cells. Since the mutation was not detected in peripheral blood leukocytes 9 months before the diagnosis, biallelic somatic inactivation of the TP53 gene might play an important role in the occurrence of MDS. His poor outcome might be associated with resistance to chemotherapy/radiation of a minor clone with both TP53 gene alteration and MLL duplication that already existed at onset.

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.