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Low GFI1 expression in white blood cells of CP–CML patients at diagnosis is strongly associated with subsequent blastic transformation

Leukemia volume 27, pages 1427–1430 (2013)Cite this article

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Chronic myeloid leukemia (CML) is characterized by the BCR–ABL1 fusion gene, resulting in uncontrolled proliferation of myeloid progenitor cells. Growth factor independence 1 (GFI1) is a transcription factor with a crucial role in haematopoiesis, including preserving haematopoietic stem cell (HSC) quiescence and enhancing granulocytic differentiation, but is not required for inducing myeloid differentiation in p210BCR/ABL-transformed cells.1 Recently, Soliera et al.2 demonstrated that ectopic GFI1 expression inhibited proliferation and colony formation both in p210BCR/ABL-expressing cell lines and in primary CD34+ CML cells through the repression of STAT5B and/or Mcl-1. This study, along with their previous work1 demonstrated the biological importance of the GFI1/STAT5B/Mcl-1 regulatory pathway on proliferation and survival of CML cells. However, the association between GFI1 expression and the achievement of response to imatinib therapy, be it major molecular response (MMR; <0.1% BCR–ABL1 (IS)) or early molecular response (BCR–ABL1 ⩽10% following 3 months of imatinib therapy) in de-novo chronic phase–CML (CP–CML) patients has not been examined. We hypothesized, based on the findings of Soliera et al. that increased GFI1 expression would be associated with a favorable outcome in CP–CML treated with imatinib.

The expression of GFI1 was examined using TaqMan Low Density array (RQ-PCR, Applied Biosystems, Carlsbad, CA, USA) in white blood cells of 40 de-novo CP–CML patients enrolled in clinical trials conducted in our Centre, who received imatinib as frontline therapy. Data analysis was performed using the statistical program R version 2.15.1, with the Bioconductor package high-throughput analysis and visualization of quantitative real-time PCR (HTqPCR)3 and GraphPad Prism 5. GFI1 expression (Hs00382207_m1, Applied Biosystems) was normalized to GUSB expression (Hs99999908_m1, Applied Biosystems) using the ΔΔCt method.4 As GFI1 is primarily expressed in granulocytes,5 we rationalized that the use of white cells would enable accurate representation of total GFI1 expression from each patient.

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Acknowledgements

DBW is supported by a PhD scholarship from the Leukemia Foundation of Australia. TPH is an NHMRC Practitioner Fellow. This project was funded by a Leukemia and Lymphoma Society (LLS) grant and a NHMRC project grant.

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Author notes

  1. C H Kok and D B Watkins: This authors contributed equally to this work.

Authors and Affiliations

  1. Haematology Department, SA Pathology (RAH Campus), Centre of Cancer Biology, Adelaide, South Australia, Australia

    C H Kok, D B Watkins, T Leclercq, R J D'Andrea, T P Hughes & D L White

  2. Department of Medicine, Centre for Personalised Cancer Medicine, University of Adelaide, Adelaide, South Australia, Australia

    C H Kok, D B Watkins, R J D'Andrea, T P Hughes & D L White

  3. Department of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia

    R J D'Andrea

  4. Faculty of Health Science, University of South Australia, Adelaide, South Australia, Australia

    D L White

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  1. C H Kok
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Correspondence to D L White.

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Kok, C., Watkins, D., Leclercq, T. et al. Low GFI1 expression in white blood cells of CP–CML patients at diagnosis is strongly associated with subsequent blastic transformation. Leukemia 27, 1427–1430 (2013). https://doi.org/10.1038/leu.2013.47

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