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CML, BCR/ABR Studies and Myeloproliferative Disorders

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

Leukemia volume 20, pages 485–490 (2006)Cite this article

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.

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Acknowledgements

We thank Ms Yumiko Oguchi (Department of Pediatrics, Shinshu University School of Medicine) for the excellent technical assistance. This work was supported by Grants-in-Aid nos. 15790521 and 11670753 from the Ministry of Education, and by Grant-in-Aid for Cancer Research (16-3) from the Ministry of Health, Labour, and Welfare of Japan.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan

    K Matsuda, E Hidaka & K Sano

  2. Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan

    S Matsuzaki, J Miki, R Yanagisawa, Y Nakazawa, K Sakashita, T Kamijo & K Koike

  3. Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, Japan

    K Asami

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  1. K Matsuda
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Correspondence to K Koike.

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Matsuda, K., Matsuzaki, S., Miki, J. et al. Chromosomal change during 6-mercaptopurine (6-MP) therapy in juvenile myelomonocytic leukemia: the growth of a 6-MP-refractory clone that already exists at onset. Leukemia 20, 485–490 (2006). https://doi.org/10.1038/sj.leu.2404106

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