Chromosomal change during 6-mercaptopurine (6-MP) therapy in juvenile myelomonocytic leukemia: the growth of a 6-MP-refractory clone that already exists at ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-03

AUTHORS

K Matsuda, S Matsuzaki, J Miki, E Hidaka, R Yanagisawa, Y Nakazawa, K Sakashita, T Kamijo, K Asami, K Sano, K Koike

ABSTRACT

Among 11 JMML children, two had an abnormal karyotype, and nine had a normal karyotype at onset. In one patient with trisomy 8 and four patients with a normal karyotype, a new clone with an aberrant karyotype emerged 1-14 months after 6-mercaptopurine (6-MP) therapy as shown by G-banding analyses. Fluorescence in situ hybridization disclosed that an abnormal clone existed in approximately 3-6% of bone marrow cells at onset or before 6-MP therapy in all the four cases examined, and increased to approximately 12-90% during the treatment. In culture with granulocyte-macrophage colony-stimulating factor, cytogenetically abnormal clones that proliferated during 6-MP therapy possessed significantly less sensitivity to the antimetabolite, compared with cells that decreased in numbers after the therapy. A PTPN11 mutation was detected in all of granulocyte-macrophage colonies irrespective of karyotypic aberration in one patient, whereas approximately 80% of erythroid colonies and 20% of mixed colonies possessed neither a PTPN11 mutation nor chromosomal abnormalities. The appearance of chromosomal aberrations shown by G-banding during 6-MP therapy in some JMML cases may result, in part, from the growth of a 6-MP-refractory clone that already exists at onset. It is possible that treatment with 6-MP promotes progression of the disease. More... »

PAGES

2404106

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.leu.2404106

DOI

http://dx.doi.org/10.1038/sj.leu.2404106

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16424864


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