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Pluridisciplinary Laboratory Clinical Correlation

The association of the TEL-AML1 chromosomal translocation with the accumulation of methotrexate polyglutamates in lymphoblasts and with ploidy in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

Leukemia volume 15, pages 1081–1088 (2001)Cite this article

Abstract

Lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia (BpALL) with chromosomal hyperdiploidy and with translocations affecting chromosome 12p11–13, accumulate high and low levels of methotrexate polyglutamates (MTXPGs), respectively. Recently a cryptic translocation, t(12;21) (p13;q22), has been demonstrated by molecular and fluorescence in situ hybridization techniques in this disease. The chimeric TEL-AML1 transcript, which has been associated with this translocation, can be detected in up to 25% of children with BpALL. We detected the TEL-AML1 and/or the AML1-TEL transcript in 30 (33%) of 91 patients studied. Levels of lymphoblast MTXPGs were lower in those with than in those without the TEL-AML1 translocation (P = 0.004). Hyperdiploidy was rare in lymphoblasts with the TEL-AML1 translocation (P = 0.047). Both ploidy (P = 0.0015) and TEL-AML1 status (P = 0.0043) were independently and significantly correlated with the log of the lymphoblast MTXPG level. However, the presence of TEL-AML1 or of hyperdiploidy accounted for only 22% of the variation of this value. Our results imply that each of 1.16 ⩾ DI and the presence of the TEL-AML1 translocation confers a 50% decrease in lymphoblast MTXPG level. When planning reduction of therapy for either of the two excellent outcome categories of hyperdiploid or TEL-AML1 BpALL, one should consider the difference between these two subgroups in the ability of lymphoblasts to accumulate MTXPGs.

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Acknowledgements

This research was supported in part by the following grants from the National Cancer Institute: CA-33587, CA-25408, CA-32053, CA-03161, CA-29139, CA-53490, CA-33625, CA-29691, CA-28841, CA-31566, CA-52317, CA-15989. In addition, it was supported by grants from the National Cancer Institute of Canada, the Cancer Research Society and the McGill University – Montreal Children's Hospital Research Institute, and assisted by the Penny Cole Fund, the Fast Foundation, the InterService Clubs Council Telethon of Stars, the Lamplighters Children's Cancer–Leukemia Association, the Children's Cancer Fund, the Debbie Saunders Fund, the friends of Ande, the Midwest Athletes against Childhood Cancer (MACC Fund), the American Lebanese Syrian Associated Charities (ALSAC) and the American Cancer Society.

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Authors and Affiliations

  1. The Penny Cole Hematology Research Laboratory, McGill University – Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada

    VM Whitehead, C Payment & M-J Vuchich

  2. Department of Pediatrics, McGill University, Montreal, PQ, Canada

    VM Whitehead

  3. Department of Medical Genetics, Baylor College of Medicine, Houston, TX, USA

    L Cooley

  4. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA

    SJ Lauer

  5. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    DH Mahoney

  6. Department of Statistics and the Pediatric Oncology Group Statistical Office, University of Florida, Gainesville, FL, USA

    JJ Shuster

  7. Department of Pediatrics, Hôpital Sainte-Justine, Montreal, QC, Canada

    ML Bernstein

  8. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    AT Look

  9. Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA

    DJ Pullen

  10. Department of Pediatrics, Midwest Children's Cancer Center and Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA

    B Camitta

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Appendix: Participating Institutions and NCI Grant Support

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Whitehead, V., Payment, C., Cooley, L. et al. The association of the TEL-AML1 chromosomal translocation with the accumulation of methotrexate polyglutamates in lymphoblasts and with ploidy in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Leukemia 15, 1081–1088 (2001). https://doi.org/10.1038/sj.leu.2402165

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