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Infants with acute lymphoblastic leukemia: no evidence for high methotrexate resistance

Leukemia volume 16, pages 949–951 (2002)Cite this article

The antifolate methotrexate (MTX) has contributed significantly to the great improvement in overall survival and central nervous system prophylaxis in patients with acute lymphoblastic leukemia (ALL) in the past 50 years. After transport into the cell, MTX is polyglutamylated with multiple glutamate residues to MTX-polyglutamates (MTX-PGs), which have superior intracellular retention. Cellular resistance to MTX might contribute to treatment failure in childhood ALL. C/preB-lineage ALL (⩾1 year) has a favorable prognosis and is in vitro more sensitive to MTX in the TSIA (short exposure) than T-lineage ALL.1 C/preB ALL also have more efficient accumulation of (long chain) MTX-PGs compared to T-ALL and acute myeloid leukemia.2,3,4

ALL diagnosed in infants less than 1 year of age is closely associated with a number of biological features, especially MLL gene (at chromosome 11q23) rearrangements and the proB (CD10-negative precursor B) immunophenotype, and still have a poor outcome.5 So far, little is known of the pharmacodynamics of MTX in infants with ALL, and the relationship thereof with the other biological characteristics frequent in infant ALL. The question then arises whether the poor prognosis of infants with ALL is associated with cellular resistance to MTX.

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Acknowledgements

This work was supported in part by the Dutch Cancer Society grant VU95–921, by St Jude Cancer Center Grant CA21765, by NIH grants R37CA36401, R01CA78224, R01CA51001, by the American Lebanese Syrian Associated Charities, and by USPHS grants CA32053 and CA29139. We wish to thank the pediatric oncological centers participating in the DCLSG, COALL, BFM and POG study groups. Karyotyping of the Dutch patients was performed by members of the Netherlands Working Party on Cancer Genetics and Cytogenetics at regional cytogenetics centers and for German childhood cases karyotyping was performed in the Oncogenetic Laboratory, Children's Hospital, University of Giessen, Germany. We thank Prof W-D Ludwig and Prof OA Haas (German and Austrian BFM, respectively) for their efforts in supplying cryopreserved samples of infants with ALL for this study. We also wish to thank Dr J Shuster, POG Statistical Office, University of Florida, Gainsville FL, for providing the clinical information for the POG samples.

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Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology VU University Medical Center, Amsterdam, The Netherlands

    NL Ramakers-van Woerden, MG Rots, CH van Zantwijk & AJP Veerman

  2. Division of Oncology/Hematology, Sophia Children's Hospital, University Hospital Rotterdam, The Netherlands

    R Pieters

  3. Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

    MG Rots, P Noordhuis & GJ Peters

  4. Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands

    HB Beverloo

  5. Dutch Childhood Leukemia Study Group, The Hague, The Netherlands

    ER van Wering

  6. Pediatric Oncology Group, The Midwest Children's Cancer Center and the Medical College of Wisconsin, Milwaukee, WI, USA

    BM Camitta

  7. Pharmaceutical Department, St Jude Children's Research Hospital, Memphis, TN, USA

    C-H Pui, MV Relling & WE Evans

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Ramakers-van Woerden, N., Pieters, R., Rots, M. et al. Infants with acute lymphoblastic leukemia: no evidence for high methotrexate resistance. Leukemia 16, 949–951 (2002). https://doi.org/10.1038/sj.leu.2402491

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