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Molecular Targets for Therapy

Molecular alterations of the IDH1 gene in AML: a Children's Oncology Group and Southwest Oncology Group study

Leukemia volume 24, pages 909–913 (2010)Cite this article

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Abstract

Recent whole-genome sequencing efforts led to the identification of IDH1R132 mutations in acute myeloid leukemia (AML) patients. We studied the prevalence and clinical implications of IDH1 genomic alterations in pediatric and adult AML. Diagnostic DNA from 531 AML patients treated on Children's Oncology Group trial COG-AAML03P1 (N=257), and Southwest Oncology Group trials SWOG-9031, SWOG-9333 and SWOG-9500 (N=274), were tested for IDH1 mutations. Codon R132 mutations were absent in the pediatric cohort, but were found in 12 of 274 adult patients (4.4%, 95% CI 2.3–7.5). IDH1R132 mutations occurred most commonly in patients with normal karyotype, and those with FLT3/ITD and NPMc mutations. Patients with IDH1R132 mutations trended toward higher median diagnostic white blood cell counts (59.2 × 109 vs 29.1 × 109 per liter, P=0.19) than those without mutations, but the two groups did not differ significantly in age, bone marrow blast percentage, overall survival or relapse-free survival. Eleven patients (2.1%) harbored a novel V71I sequence alteration, which was found to be a germ-line polymorphism. IDH1 mutations were not detected in pediatric AML, and are uncommon in adult AML.

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Acknowledgements

We thank the patients and families who consented to the use of biologic specimens in these trials. We also thank the AML Reference Laboratories of the COG and SWOG for providing diagnostic specimens, and Dr Cherise Guess for scientific editing. This work was supported by the National Institutes of Health (Grants No. K23 CA92405, CA18029, CA32102, CA114563, R01 CA114563-01, R21 CA102624, R21 CA10262-01, U10 CA032102-30, CA38926, CA20319, CA27057, CA12213 and Children's Oncology Group Chair's Grant NIH U10 CA98543).Authorship: PH designed research, performed research, analyzed data and wrote the article. TAA and KJK served as senior statisticians, performed statistical analyses and edited the article. KLM, JK and RZ performed research and edited the article. RBG performed statistical analyses and edited the article. SCR, BAH, VO, CAH, JLF, ASG, SHP, JEA, GHR, LB, CLW, IDB, JPR, FRA and DLS analyzed data and edited the article. SM designed research, analyzed data and wrote the article.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    P A Ho, K L Miller, J Kuhn, R Zeng, V Oehler, I D Bernstein, J P Radich, F R Appelbaum, D L Stirewalt & S Meshinchi

  2. Division of Pediatric Hematology/Oncology, University of Washington School of Medicine, Seattle, WA, USA

    P A Ho, I D Bernstein & S Meshinchi

  3. Department of Biostatistics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    T A Alonzo

  4. Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    K J Kopecky

  5. Biostatistics, Children's Oncology Group, Arcadia, CA, USA

    R B Gerbing

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

    S C Raimondi

  7. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    B A Hirsch

  8. Division of Medical Oncology, Seattle Cancer Care Alliance, University of Washington School of Medicine, Seattle, WA, USA

    V Oehler, S H Petersdorf, J P Radich, F R Appelbaum & D L Stirewalt

  9. Clinical Development, Reata Pharma, Dallas, TX, USA

    C A Hurwitz

  10. Department of Pediatrics, University of Southern California, Los Angeles, CA, USA

    J L Franklin

  11. Amgen Incorporated, Thousand Oaks, CA, USA

    J L Franklin

  12. Division of Hematology/Oncology, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA

    A S Gamis

  13. Katmai Oncology Group, Anchorage, AK, USA

    J E Anderson

  14. School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA

    G H Reaman

  15. School of Medicine, University of Michigan, Ann Arbor, MI, USA

    L H Baker

  16. UNM Cancer Research Facility, University of New Mexico Cancer Research and Treatment Center, Albuquerque, NM, USA

    C L Willman

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  1. P A Ho
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  2. T A Alonzo
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  4. K L Miller
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  5. J Kuhn
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  6. R Zeng
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  7. R B Gerbing
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  9. B A Hirsch
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  10. V Oehler
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  11. C A Hurwitz
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  12. J L Franklin
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  13. A S Gamis
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  14. S H Petersdorf
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  15. J E Anderson
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  16. G H Reaman
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  17. L H Baker
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  18. C L Willman
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  19. I D Bernstein
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  20. J P Radich
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  21. F R Appelbaum
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  22. D L Stirewalt
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  23. S Meshinchi
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Corresponding author

Correspondence to S Meshinchi.

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Ho, P., Alonzo, T., Kopecky, K. et al. Molecular alterations of the IDH1 gene in AML: a Children's Oncology Group and Southwest Oncology Group study. Leukemia 24, 909–913 (2010). https://doi.org/10.1038/leu.2010.56

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  • DOI: https://doi.org/10.1038/leu.2010.56

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