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Characteristics of chronic lymphocytic leukemia with somatically acquired mutations in NOTCH1 exon 34

Leukemia volume 26, pages 1108–1110 (2012)Cite this article

The pathogenesis of chronic lymphocytic leukemia (CLL) remains incompletely understood.1 This includes the level of understanding of the role of single gene mutations in CLL biology and clinical behavior, and knowledge in this area is evolving.2, 3 Recently, using massively parallel sequencing, stabilizing mutations in NOTCH1 were identified in CLL,4 and preliminary associations of NOTCH1 mutations and CLL disease characteristics were reported. The latter included detection of an enrichment of NOTCH1 mutations in IgVH unmutated CLL, results indicating worse overall survival (OS) and an association of NOTCH1 exon 34 mutations with disease transformation (Richter's transformation).5

To complement existing knowledge of the frequency, characteristics and clinical impact of NOTCH1 exon 34 mutations in CLL, and to provide guidance for future research, we resequenced NOTCH1 exon 34 in a well-characterized, prospectively enrolled cohort of 257 CLL patients, of which 200 were untreated and 57 relapsed at study enrollment.6 Sequence analysis using Sanger sequencing was performed on DNA isolated from FACS-sorted CD19+ cells, cryopreserved at the time of study enrollment. The somatic nature of mutations was confirmed using paired DNA isolated from FACS-sorted CD3+ cells.

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References

  1. Chiorazzi N, Rai KR, Ferrarini M . Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804–815.

    Article  CAS  Google Scholar 

  2. Brown JR, Levine RL, Thompson C, Basile G, Gilliland DG, Freedman AS . Systematic genomic screen for tyrosine kinase mutations in CLL. Leukemia 2008; 22: 1966–1969.

    Article  CAS  Google Scholar 

  3. Zhang X, Reis M, Khoriaty R, Li Y, Ouillette P, Samayoa J et al. Sequence analysis of 515 kinase genes in chronic lymphocytic leukemia. Leukemia 2011; e-pub ahead of print 24 June 2011; doi:10.1038/leu.2011.163.

    Article  CAS  Google Scholar 

  4. Puente XS, Pinyol M, Quesada V, Conde L, Ordonez GR, Villamor N et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011; 475: 101–105.

    Article  CAS  Google Scholar 

  5. Fabbri G, Rasi S, Rossi D, Trifonov V, Khiabanian H, Ma J et al. Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med 2011; 208: 1389–1401.

    Article  CAS  Google Scholar 

  6. Ouillette P, Collins R, Shakhan S, Li J, Peres E, Kujawski L et al. Acquired genomic copy number aberrations and survival in chronic lymphocytic leukemia. Blood 2011; 118: 3051–3061.

    Article  CAS  Google Scholar 

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Acknowledgements

Supported by a National Institutes of Health Grants CA136537 (SM) and the Translational Research Program of the Leukemia and Lymphoma Society of America (SM). We are grateful for services provided by the microarray core of the University of Michigan Comprehensive Cancer Center.

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Authors and Affiliations

  1. Department of Statistics, University of Michigan, Ann Arbor, MI, USA

    K Shedden & S N Malek

  2. Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA

    Y Li, P Ouillette & S N Malek

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  1. K Shedden
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  2. Y Li
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  3. P Ouillette
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  4. S N Malek
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Correspondence to S N Malek.

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Shedden, K., Li, Y., Ouillette, P. et al. Characteristics of chronic lymphocytic leukemia with somatically acquired mutations in NOTCH1 exon 34. Leukemia 26, 1108–1110 (2012). https://doi.org/10.1038/leu.2011.361

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