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MicroRNAs and deletion of the derivative chromosome 9 in chronic myeloid leukemia

Leukemia volume 23, pages 186–188 (2009)Cite this article

MicroRNAs (miRNAs) attenuate gene expression by pairing with the 3′ UTR of target transcripts inducing RNA cleavage or translational inhibition. These small regulatory molecules are central to various physiologic processes and their disruption is associated with human diseases, particularly cancer.1 MiRNAs map predominantly to fragile sites in the genome, and gain or loss of chromosomal material may result in a miRNA deregulation.2 In hematological malignancies, amplification of chromosome 13q31 in B-cell lymphomas leads to overexpression of the miRNA cluster 17–923 and deletion of chromosome 13q14 in chronic lymphoid leukemia has been linked to downregulation of miR-15a and miR16-1.4, 5

To define the potential involvement of these miRNAs in the pathogenesis of CML with der(9q) deletion, we identified a collection of 48 t(9;22)-positive CML cases and used fluorescence in situ hybridization to ascertain their der(9q) status. Five CML cell lines, which either lacked ABL-BCR expression (K562, CMLT1, SD1 and TK6) or is known to have a der(9q) deletion (MC3)9 were also studied. All cases were investigated with the BCR-ABL dual-color/dual-fusion probe system (Abbott Molecular, IL, USA) as well as with three bacterial artificial chromosome (BAC) clones (RP11-395P17, RP11-339B21 and RP11-409K20—BACPAC Resources Center, Oakland, CA, USA) mapping centromeric to the ABL locus. Importantly, two of these probes specifically included miR-219-2 or miR-199b sequences (Figure 1a). BAC DNAs were isolated and hybridized to the patient's slides as we described previously.10 Using this strategy, we found der(9q) deletion in 7 (14.5%) of the 48 CML patients analyzed. In two samples, the deletion extended as far centromeric as to include both miRNA loci (Figure 1b); there were no instances of deletion of miR-219-2 or 199b in samples with an otherwise intact der(9q). We confirmed the der(9q) deletion in MC3 but the miRNA loci were preserved in this cell line. All the other cell lines showed multiple copies of normal chromosome 9 and der(9) and the status of the miRNA loci could not be ascertained (data not shown). Thus, these data confirmed the idea that these miRNAs could be targeted in CML cases that harbor large der(9q) deletion.

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References

  1. Bartel DP . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281–297.

    Article  CAS  PubMed  Google Scholar 

  2. Esquela-Kerscher A, Slack FJ . Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 2006; 6: 259–269.

    Article  CAS  PubMed  Google Scholar 

  3. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S et al. A microRNA polycistron as a potential human oncogene. Nature 2005; 435: 828–833.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99: 15524–15529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fulci V, Chiaretti S, Goldoni M, Azzalin G, Carucci N, Tavolaro S et al. Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood 2007; 109: 4944–4951.

    Article  CAS  PubMed  Google Scholar 

  6. Fourouclas N, Campbell PJ, Bench AJ, Swanton S, Baxter EJ, Huntly BJ et al. Size matters: the prognostic implications of large and small deletions of the derivative 9 chromosome in chronic myeloid leukemia. Haematologica 2006; 91: 952–955.

    CAS  PubMed  Google Scholar 

  7. Kreil S, Pfirrmann M, Haferlach C, Waghorn K, Chase A, Hehlmann R et al. Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia. Blood 2007; 110: 1283–1290.

    Article  CAS  PubMed  Google Scholar 

  8. Rai D, Karanti S, Jung I, Dahia PL, Aguiar RC . Coordinated expression of microRNA-155 and predicted target genes in diffuse large B-cell lymphoma. Cancer Genet Cytogenet 2008; 181: 8–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Reid AG, Tarpey PS, Nacheva EP . High-resolution analysis of acquired genomic imbalances in bone marrow samples from chronic myeloid leukemia patients by use of multiple short DNA probes. Genes Chromosomes Cancer 2003; 37: 282–290.

    Article  CAS  PubMed  Google Scholar 

  10. Wilkinson K, Velloso ER, Lopes LF, Lee C, Aster JC, Shipp MA et al. Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib. Blood 2003; 102: 4187–4190.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by a grant from the Department of Defense (CM050018) to RCTA. Ricardo CT Aguiar is a Scholar of the American Society of Hematology.

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  1. Division of Hematology and Medical Oncology, Department of Medicine, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    S Karanti, D Rai, T Oh & R C T Aguiar

  2. Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    A Chaubey & S G Adhvaryu

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Correspondence to R C T Aguiar.

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Chaubey, A., Karanti, S., Rai, D. et al. MicroRNAs and deletion of the derivative chromosome 9 in chronic myeloid leukemia. Leukemia 23, 186–188 (2009). https://doi.org/10.1038/leu.2008.154

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