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Downregulated expression of genes mapping on chromosome 9 in chronic myeloid leukemia cases bearing genomic deletions on der(9)

Leukemia volume 23, pages 813–816 (2009)Cite this article

Genomic deletions flanking the breakpoint on der(9)t(9;22) occur in 10–18% of patients with chronic myeloid leukemia (CML). These microdeletions have a variable extension and involve sequences on chromosomes 9 and/or 22, located proximally to the ABL and distally to the BCR gene.1 The deletions on der(9) are associated with a poor prognosis of interferon-α (IFN-α) therapy, whereas controversial data about their influence on the response to imatinib are available.2, 3 The molecular mechanisms responsible for this unfavorable prognosis are still unclear. The most probable hypothesis is that microdeletions could be associated with the loss of tumor suppressor genes or genes implicated in cell-cycle regulation, resulting in a proliferative advantage of the leukemic clone.4 This phenomenon may act by a gene dosage effect known as haploinsufficiency: mutation or loss of a single allele may be sufficient to elicit a cellular phenotype that leads to tumorigenesis without the inactivation of the second allele.

The aim of our study was therefore to assess whether the sequences loss on der(9) in CML patients was associated with a gene product decrease. To date, an expression study of genes mapping within the deleted regions on der(9) has never been performed. We have reported earlier a detailed molecular cytogenetic characterization of 60 (18%) out of 334 CML patients, using panels of bacterial artificial chromosome clones mapping next to the t(9;22) breakpoint.5 We showed that the extent of the genomic deletion on der(9) ranged from a few hundred kilobases to many megabases, causing the loss of several genes with a known function.

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Acknowledgements

We thank Ms MVC Pragnell, BA, for language revision of the paper. The financial support of Associazione Italiana contro le Leucemie (AIL)-BARI is gratefully acknowledged. AZ was supported by fellowship of the Società Italiana di Ematologia Sperimentale (SIES).

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Author notes

  1. F Albano, L Anelli and A Zagaria: These authors contributed equally to this work.

  2. M Rocchi and G Specchia: These authors share the seniorship of this article.

Authors and Affiliations

  1. Department of Hematology, University of Bari, Bari, Italy

    F Albano, L Anelli, A Zagaria, A Pannunzio, V Liso & G Specchia

  2. Department of Genetics and Microbiology, University of Bari, Bari, Italy

    M Rocchi

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  1. F Albano
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  2. L Anelli
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  7. G Specchia
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Correspondence to F Albano.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Albano, F., Anelli, L., Zagaria, A. et al. Downregulated expression of genes mapping on chromosome 9 in chronic myeloid leukemia cases bearing genomic deletions on der(9). Leukemia 23, 813–816 (2009). https://doi.org/10.1038/leu.2008.311

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