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BRAF mutations in chronic lymphocytic leukemia

BRAF mutations have been shown to occur at a high frequency in melanoma and thyroid cancer, but also at lower frequencies in hematological malignancies. To assess the potential role of BRAF, we have sequenced exons 11 and 15 of BRAF in 138 cases with chronic lymphocytic leukemia (CLL) and 32 cases o...

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Main Authors: Jebaraj, Billy Michael Chelliah (Author) , Kienle, Dirk Lars (Author) , Bühler, Andreas (Author) , Winkler, Dirk (Author) , Döhner, Hartmut (Author) , Stilgenbauer, Stephan (Author) , Zenz, Thorsten (Author)
Format: Article (Journal)
Language:English
Published: 2013
In: Leukemia and lymphoma
Year: 2012, Volume: 54, Issue: 6, Pages: 1177-1182
ISSN:1029-2403
DOI:10.3109/10428194.2012.742525
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3109/10428194.2012.742525
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Author Notes:Billy Michael Chelliah Jebaraj, Dirk Kienle, Andreas Bühler, Dirk Winkler, Hartmut Döhner, Stephan Stilgenbauer & Thorsten Zenz

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520 |a BRAF mutations have been shown to occur at a high frequency in melanoma and thyroid cancer, but also at lower frequencies in hematological malignancies. To assess the potential role of BRAF, we have sequenced exons 11 and 15 of BRAF in 138 cases with chronic lymphocytic leukemia (CLL) and 32 cases of B-cell prolymphocytic leukemia (B-PLL). We found an incidence of BRAF mutations of 2.8% in CLL (4/138), while no cases with B-PLL showed BRAF mutations. The analysis of a cohort of patients with fludarabine-refractory disease (n = 87) showed no increase in the mutation incidence, suggesting that this mutation is not selected for during the disease progression. A limited analysis of the effect of BRAF inhibition in primary CLL cells showed no cell death induction in CLL samples with and without BRAF mutations. Our analysis suggests that BRAF mutations occur at a low frequency in CLL. The pharmacological inhibition of MEK/ERK signaling using the mutant BRAF inhibitor PLX4720 showed no effect on viability in vitro in CLL cases. 
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