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

P. A. Ho, T. A. Alonzo, K. J. Kopecky, K. L. Miller, J. Kuhn, R. Zeng, R. B. Gerbing, S. C. Raimondi, B. A. Hirsch, V. Oehler, C. A. Hurwitz, J. L. Franklin, A. S. Gamis, S. H. Petersdorf, J. E. Anderson, G. H. Reaman, L. H. Baker, C. L. Willman, I. D. Bernstein, J. P. RadichF. R. Appelbaum, D. L. Stirewalt, S. Meshinchi

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

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). IDH1 R132 mutations occurred most commonly in patients with normal karyotype, and those with FLT3/ITD and NPMc mutations. Patients with IDH1 R132 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.

Original languageEnglish (US)
Pages (from-to)909-913
Number of pages5
JournalLeukemia
Volume24
Issue number5
DOIs
StatePublished - May 2010

Bibliographical note

Funding Information:
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).

Keywords

  • Acute myeloid leukemia
  • FLT3
  • IDH1
  • Isocitrate dehydrogenase
  • NPM
  • Pediatric AML

Fingerprint

Dive into the research topics of 'Molecular alterations of the IDH1 gene in AML: A Children's Oncology Group and Southwest Oncology Group study'. Together they form a unique fingerprint.

Cite this