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Myeloid progenitors with PTPN11 and nonRAS pathway gene mutations are refractory to treatment with 6-mercaptopurine in juvenile myelomonocytic leukemia

Leukemia volume 28, pages 1545–1548 (2014)Cite this article

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Juvenile myelomonocytic leukemia (JMML) is a fatal, mixed myeloproliferative and myelodysplastic disorder occurring in infancy and early childhood. Children with JMML have mutually exclusive genetic abnormalities in granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathways, inactivation of the NF1 or mutations in PTPN11, NRAS, KRAS and CBL.1, 2 A whole-exome sequencing study, performed by Sakaguchi et al.,3 has recently demonstrated that in addition to the high frequency of RAS pathway mutations, mutations in SETBP1 and JAK3 are common recurrent secondary events, and that these events may be involved in tumor progression, and are associated with poor clinical outcomes. The SETBP1 and JAK3 mutations have also been reported in the other hematological malignancies.4, 5, 6, 7, 8, 9

We have previously reported seven cases of patients (five with PTPN11 mutation; one with NRAS mutation) with significant chromosomal changes after chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT).10 In addition, we observed a loss of wild-type NRAS locus and monosomy 7 after blastic crisis in a patient with JMML and a heterozygous NRAS mutation.11

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Acknowledgements

We thank Ms Yumiko Oguchi, Department of Pediatrics, Shinshu University School of Medicine, for her technical support.

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Authors and Affiliations

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

    K Matsuda, C Iwashita & T Honda

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

    Y Nakazawa, T Kurata, K Hirabayashi, S Saito, M Tanaka, K Yoshikawa, R Yanagisawa, K Sakashita & K Koike

  3. Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki, Japan

    S Sasaki

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  1. K Matsuda
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Correspondence to K Koike.

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Author Contributions

KK and KM designed and performed the research, collected the samples, analyzed the data and wrote the paper. YN designed the research. CI performed the research. TK, KH, SS, MT, KY, RY, KS and SS collected the samples and analyzed the data. All the authors read and approved the manuscript.

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Matsuda, K., Nakazawa, Y., Iwashita, C. et al. Myeloid progenitors with PTPN11 and nonRAS pathway gene mutations are refractory to treatment with 6-mercaptopurine in juvenile myelomonocytic leukemia. Leukemia 28, 1545–1548 (2014). https://doi.org/10.1038/leu.2014.58

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