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Double minute chromosomes and c-MYC amplification in a child with secondary myelodysplastic syndrome after treatment for acute lymphoblastic leukemia

Leukemia volume 14, pages 1314–1315 (2000)Cite this article

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Double minutes (dmins) and homogeneously staining regions (hsrs) are found in a wide range of tumors and are generally associated with gene amplification,1 disease progression, drug resistance, and often a poor prognosis.2 Dmins and hsrs are mostly seen in solid tumors.1 Even though reports of dmins are rare in leukemia, a number of studies have shown that the frequency varies, from less than 1% to 12.5%.34 However, with the advent of banding techniques, fewer cases with dmins have been reported. This is likely due to the trypsin treatment used in G-banding. Dmins have been described mostly in elderly patients with leukemias. To date, only one case of childhood leukemia (secondary T cell ALL) with dmins and other chromosomal abnormalities has been reported.5 Most of the dmins described in leukemia are the result of amplification of the c-MYC gene.6 We report the first case of a secondary myelodysplastic syndrome (MDS) with dmins and c-MYC amplification in a child after chemotherapy for acute lymphoblastic leukemia (ALL).

An 11-year-old girl was initially seen because of bruising and facial paralysis on the right side. Laboratory work-up revealed 11% blasts in the peripheral blood. A bone marrow aspirate demonstrated complete replacement by malignant lymphoblasts. Immunophenotyping by flow cytometry was consistent with a diagnosis of pre-B ALL; no coexpression of myeloid markers was observed. The DNA Index was 0.77 and 1.46 corresponding to the hypodiploid and hyperdiploid lines observed by cytogenetics. The patient was enrolled in the high-risk arm of the leukemia protocol at our institution. Because of leukemic CNS involvement at diagnosis, the patient also received radiation therapy to the base of skull (total dose, 12 Gy). The patient received induction chemotherapy with vincristine, prednisone, daunamycin, L-asparaginase, high-dose 6-mercaptopurine, and intrathecal methotrexate, hydrocortisone and cytarabine. Therapy was complicated by severe avascular necrosis of both femoral heads and herpes simplex keratitis. She had full resolution of her neurologic deficit and maintained complete continuous remission until the time of relapse.

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Acknowledgements

We thank E Entrekin, J Dalton, P Mardis, R Marion, A Washington and T Motroni for technical assistance. We also thank JC Jones for scientific editing.

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Authors and Affiliations

  1. Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA

    S Mathew, RB Lorsbach & SC Raimondi

  2. Department of Hematology and Oncology, St Jude Children's Research Hospital, Memphis, TN, USA

    P Shearer & JT Sandlund

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  1. S Mathew
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Mathew, S., Lorsbach, R., Shearer, P. et al. Double minute chromosomes and c-MYC amplification in a child with secondary myelodysplastic syndrome after treatment for acute lymphoblastic leukemia. Leukemia 14, 1314–1315 (2000). https://doi.org/10.1038/sj.leu.2401782

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