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Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic leukemia (CLL): a study on 852 patients

Leukemia volume 27, pages 2393–2396 (2013)Cite this article

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Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Recently, recurrent activating mutations of NOTCH1 have been reported in up to 12% of CLL patients, underlining the relevance of NOTCH1 mutations (NOTCH1mut) as an independent negative prognostic marker.1, 2, 3 NOTCH1mut in CLL are known to be located predominantly within the C-terminal PEST domain, frequently resulting in a truncated protein that is more stable than the wild-type one and activates the NOTCH1 signaling pathway.3

The aim of this study was to determine the frequency and prognostic impact of NOTCH1mut in CLL and to evaluate the range of mutational burden. We used the massively parallel amplicon next-generation deep-sequencing (NGS) technology (454 Life Sciences, Branford, CT, USA), enabling us to detect also low-level mutational clones, which have not been studied in detail yet. We here investigated a large unselected cohort of adult CLL patients for mutations in NOTCH1.

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Acknowledgements

Part of the sequencing of +12 cohorts was supported by Roche Applied Science (Penzberg, Germany). NOTCH1 mutation analyses were performed using oligonucleotide primer plates designed as part of the IRON-II collaborative network of hematological laboratories applying 454 amplicon next-generation deep-sequencing.15

Author contributions

SW, AK and SS designed the study. SW, SJ, MH, MA and VG performed research and generated data. SW, AR and AK analyzed and interpreted the data. JMH-R contributed clinical data. CH, WK, TH and SS performed diagnostic assessment and contributed to clinical data. SW wrote the paper.

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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    S Weissmann, A Roller, S Jeromin, V Grossmann, C Haferlach, W Kern, T Haferlach, S Schnittger & A Kohlmann

  2. IBSAL, IBMCC, Centro de Investigacion del Cancer, Universidad de Salamanca-CSIC, Salamanca, Spain

    M Hernández, M Abáigar & J M Hernández-Rivas

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  1. S Weissmann
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  2. A Roller
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  3. S Jeromin
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  5. M Abáigar
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  6. J M Hernández-Rivas
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  7. V Grossmann
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  8. C Haferlach
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  9. W Kern
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  11. S Schnittger
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  12. A Kohlmann
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Corresponding author

Correspondence to S Weissmann.

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Competing interests

SW, AR, SJ, VG and AK are employed by the MLL Munich Leukemia Laboratory. WK, SS, CH and TH are part owners of the MLL Munich Leukemia Laboratory. MH, MA and JMH-R declare no conflict of interest.

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Weissmann, S., Roller, A., Jeromin, S. et al. Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic leukemia (CLL): a study on 852 patients. Leukemia 27, 2393–2396 (2013). https://doi.org/10.1038/leu.2013.218

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