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Preferential expression of the transcription coactivator HTIF1α gene in acute myeloid leukemia and MDS-related AML

Leukemia volume 16, pages 886–893 (2002)Cite this article

Abstract

HTIF1α, a transcription coactivator which is able to mediate RARα activity and functionally interact with PML, is encoded by a gene on chromosome 7q32–34, which is a critical region in acute myeloid leukemias (AML). With the assumption that this gene may be related to AML, we investigated the HTIF1α DNA structure and RNA expression in leukemic cells from 36 M1–M5 AML patients (28 ‘de novo’ and eight ‘secondary’ to myelodysplastic syndrome (MDS)). Abnormal HTIF1α DNA fragments were never found, whereas loss of HTIF1α DNA was observed in the patients with chromosome 7q32 deletion and translocation, and in one case without detectable chromosome 7 abnormality. HTIF1α RNA was found in acute myelocytic leukemic blasts, and was almost undetectable in normal mononuclear cells. The expression varied among the patients: higher in M1 to M3 subtypes, with the highest values in M1; low levels were constantly observed in M4 and M5 AML. In addition, HTIF1α was significantly overexpressed in MDS-related AML (MDR-AML), but not in MDS. We also found that HTIF1α expression was high in myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells, induced to differentiate along the monocytic–macrophage pathway by TPA or vitamin D3, HTIF1α expression decreased, whereas it was maintained at high levels on induction to granulocytic differentiation by RA or DMSO. In K562 cells, HTIF1α RNA levels did not change after hemin-induced erythroid differentiation. These results suggest that HTIF1α could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages.

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Acknowledgements

We would like to thank Dr Valeria Bertagnolo for kindly providing us with HL60 and NB4 cells. The work is supported by MURST Cofin, AIRC coordinated grant to AC, and ex-60%. DG is a recipient of a Cofin fellowship, CDA is a recipient of a FIRC fellowship.

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Authors and Affiliations

  1. Centro di Biotecnologie, Sezione di Studi Biochimici, Università degli Studi di Ferrara, Ferrara, Italy

    D Gandini & C De Angeli

  2. Dipartimento di Scienze Biomediche e Terapie Avanzate, Sezione di Ematologia, Università degli Studi di Ferrara, Ferrara, Italy

    D Gandini, C De Angeli, F Lanza, A Cuneo & GL Castoldi

  3. Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Ferrara, Ferrara, Italy

    G Aguiari, E Manzati & L del Senno

  4. Centro Interdipartimentale di Ricerca sul Cancro, Università degli Studi di Ferrara, Ferrara, Italy

    A Cuneo & L del Senno

  5. Molecular Biology Program, and Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    PP Pandolfi

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Gandini, D., De Angeli, C., Aguiari, G. et al. Preferential expression of the transcription coactivator HTIF1α gene in acute myeloid leukemia and MDS-related AML. Leukemia 16, 886–893 (2002). https://doi.org/10.1038/sj.leu.2402452

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