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In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels

Leukemia volume 25, pages 733–736 (2011)Cite this article

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A Corrigendum to this article was published on 14 December 2011

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Chromosomal rearrangements are frequently found in hematological malignancies.1 Transgenic expression of the generated aberrant transcripts and corresponding fusion proteins often induces leukemia in mice, suggesting a role in disease onset.2

The MYB gene, on human chromosome 6, corresponds to a 75-kDa transcription factor exerting a physiological function in the hematopoietic system (reviewed in Ramsay and Gonda3). GATA1, a nuclear protein with an essential role in hematopoiesis, is coded by a gene located on the human X chromosome (reviewed in Shimizu et al.4). A specific and complementary cross talk between these two factors has been observed in hematopoietic maturation. High levels of MYB and low levels of GATA1 characterize the early stages of hematopoiesis: as differentiation progresses, an inverse regulation takes place ultimately leading to high levels of GATA1 and low levels of MYB in terminally differentiated cells.3 The role of MYB and GATA1 has been explored through various in vivo studies. Several animal models that expressed reduced levels of GATA1 were used to study the effects of its deficiency. Interestingly, expression of the GATA1low allele, as obtained in one GATA1 genetically impaired mouse model, results in anemia and thrombocytopenia,5 and eventually into a disease closely resembling human idiophatic myelofibrosis.6

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Acknowledgements

This work was supported by AIRC (Associazione Italiana per la Ricerca sul Cancro) and Eredità Benilde Viotti. We are grateful to Stuart H Orkin and Zhe Li for providing the GATA1low mice; Loris Bernard and Sara Volorio for technical assistance; Alberto Gobbi and Massimo Stendardo for technical assistance with mice; the Cell Biology/Tissue Culture Unit for assistance with cell cultures; Patrizia Gasparini for technical assistance with FISH experiments; and Paola Dalton for manuscript editing and the CHORI BAC-PAC Resource Center, for genomic clones used in FISH experiments.

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Author notes

  1. E Belloni and D Shing: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

    E Belloni, D Shing, C Tapinassi, A Viale, O Malazzi, E Gerbino & P Giuseppe Pelicci

  2. IFOM-IEO (FIRC Institute of Molecular Oncology Foundation, European Institute of Oncology) Campus, Milan, Italy

    E Belloni, D Shing, C Tapinassi, A Viale, O Malazzi, E Gerbino, V Dall'Olio & P Giuseppe Pelicci

  3. European Institute of Oncology, Laboratory of Hemato-Oncology, Milan, Italy

    P Mancuso & F Bertolini

  4. Cogentech, IFOM-IEO (FIRC Institute of Molecular Oncology Foundation, European Institute of Oncology) Campus, Milan, Italy

    V Dall'Olio

  5. Department of Hematology, Hospital Donostia, San Sebastian, Spain

    I Egurbide

  6. Department of Genetics, University of Navarra, Pamplona, Spain

    M D Odero

  7. Division of Oncology, Center for Applied Medical Research, University of Navarra, Pamplona, Spain

    M D Odero

  8. Dipartimento di Medicina, Universita' degli Studi di Milano, Chirurgia e Odontoiatria, Milan, Italy

    P Giuseppe Pelicci

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  1. E Belloni
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Correspondence to E Belloni.

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Belloni, E., Shing, D., Tapinassi, C. et al. In vivo expression of an aberrant MYB-GATA1 fusion induces leukemia in the presence of GATA1 reduced levels. Leukemia 25, 733–736 (2011). https://doi.org/10.1038/leu.2010.317

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