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A transcriptome-wide approach reveals the key contribution of NFI-A in promoting erythroid differentiation of human CD34+ progenitors and CML cells

Leukemia volume 24, pages 1220–1223 (2010)Cite this article

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Nuclear factor I-A (NFI-A) is a member of the NFI family of transcription factors, composed of four separate genes (Nfia, Nfib, Nfic, Nfix) with distinct functions depending on the cell type and target promoter context.1, 2 Recent studies showed a novel and considerable role for NFI-A in the specification of hematopoietic lineages from CD34+ human hematopoietic progenitor cells (HPCs). In particular, NFI-A was shown to promote the erythroid lineage at the expense of the granulocytic lineage, by direct repression of the G-CSF receptor (G-CSFR) gene, and to activate β-globin transcription in normal erythroblasts and remarkably in K562 chronic myeloid leukemia (CML) cells, which do not express endogenous β-globin.2 Notably, NFI-A expression is shut off to allow terminal granulocytic or monocytic differentiation by the activity of microRNA-223 and microRNA-424, respectively,3, 4 further indicating a common negative regulatory role for NFI-A in the myeloid lineage.

In line with these findings, we recently reported that exogenous NFI-A expression in K562 CML blast crisis cells resulted in a dramatic restoration of the normal erythroid program and increased differentiation responsiveness to the anti-metabolite cytosine arabinoside (Ara-C).2 Notably, during Ara-C-induced differentiation of K562 wild-type cells, no NFI-A protein upregulation was observed compared to the physiological erythroid program of human HPCs, which is normally accompanied by increased NFI-A accumulation.2 Altogether this evidence suggests a defective tumor suppressor-like function of NFI-A in K562 CML cells. In fact, a recent study performed using array-comparative genomic hybridization and DNA sequencing reported structural alterations of the NFI-A gene associated with different chronic malignant myeloid diseases.5

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Acknowledgements

This work was supported by grants from the Italian Association for Cancer Research (AIRC) to CN and CP; University of Roma ‘La Sapienza’ and Ministero dell’Istruzione, Università e Ricerca.

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Author notes

  1. L M Starnes and A Sorrentino: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Histology and Medical Embryology, University ‘La Sapienza’, Rome, Italy

    L M Starnes & C Nervi

  2. Institute of cell biology and tissue engineering, San Raffaele Biomedical Park Foundation, Rome, Italy

    L M Starnes & C Nervi

  3. Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

    A Sorrentino & E Pelosi

  4. Department of Experimental and Diagnostic Medicine, University of Ferrara, Perrara, Italy

    M Ferracin & M Negrini

  5. Division of Hematology-Oncology, IRCCS MultiMedica, Milan, Italy

    C Peschle

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  1. L M Starnes
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  2. A Sorrentino
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  3. M Ferracin
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  4. M Negrini
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  5. E Pelosi
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  6. C Nervi
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Correspondence to C Nervi.

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Starnes, L., Sorrentino, A., Ferracin, M. et al. A transcriptome-wide approach reveals the key contribution of NFI-A in promoting erythroid differentiation of human CD34+ progenitors and CML cells. Leukemia 24, 1220–1223 (2010). https://doi.org/10.1038/leu.2010.78

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