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IDH2 somatic mutations in chronic myeloid leukemia patients in blast crisis

Leukemia volume 25, pages 178–181 (2011)Cite this article

Subjects

We read with interest a series of manuscripts,1, 2, 3, 4, 5, 6 reporting somatic mutations of the isocitrate dehydrogenase 1 and 2 enzyme isoforms (IDH1, IDH2) in patients with de novo acute myeloid leukemia (AML), in patients with chronic and blast phase Philadelphia chromosome-negative (Ph–) myeloproliferative neoplasms (MPNs) and in patients with early and accelerated phase myelodysplastic syndromes (MDSs).

We have recently screened, by massively parallel sequencing, the transcriptome of a Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) patient. The patient was a 62-year-old female diagnosed with Ph+ p210BCR−ABL-positive CML, high risk according to both Sokal (2.4) and Euro (1704.39) scores. No additional chromosomal abnormalities were detected at diagnosis by chromosome banding analysis. The patient was enrolled on a phase 2 study of nilotinib 400 mg twice daily as first line treatment of CML.7 She achieved a major molecular response (BCR-ABL/ABL=0.1% according to the International Scale) after 3 months, but suddenly progressed to lymphoid blast crisis (BC) after 6 months from diagnosis. At that time, mutation screening of the Abl kinase domain performed by Sanger sequencing showed evidence of a nilotinib-resistant T315I mutation, whereas no additional chromosomal abnormalities were detectable. The patient died of her disease 1 month, thereafter. After having obtained written informed consent from her next of kin, we retrieved the samples collected at diagnosis, at the time of major molecular response and at the time of disease progression, isolated messenger RNA and proceeded to massively parallel sequencing on a Solexa Illumina Genome Analyzer II platform according to manufacturer's instructions.

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Figure 1

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Acknowledgements

Supported by European LeukemiaNet, AIL, PRIN, Fondazione del Monte di Bologna e Ravenna.

Author information

Authors and Affiliations

  1. Department of Hematology/Oncology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy

    S Soverini, I Iacobucci, A Poerio, A Lonetti, A Gnani, S Colarossi, A Ferrari, F Castagnetti, G Rosti, M Baccarani & G Martinelli

  2. Salisbury and Human Genetics Division, Wessex Regional Genetics Laboratory, Wessex Regional Genetics Laboratory, University of Southampton School of Medicine, Southampton, UK

    J Score & N C P Cross

  3. Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain

    F Cervantes

  4. Department of Hematology/Oncology, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

  5. Department of Biotechnology, University of Verona, Verona, Italy

    M Delledonne & A Ferrarini

  6. Department of Experimental and Evolutionary Biology, Anthropology Area, University of Bologna, Bologna, Italy

    M Sazzini & D Luiselli

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Correspondence to S Soverini.

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Soverini, S., Score, J., Iacobucci, I. et al. IDH2 somatic mutations in chronic myeloid leukemia patients in blast crisis. Leukemia 25, 178–181 (2011). https://doi.org/10.1038/leu.2010.236

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