BRAF mutations in chronic lymphocytic leukemia.

Abstract:

: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.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Jebaraj BM,Kienle D,Bühler A,Winkler D,Döhner H,Stilgenbauer S,Zenz T

doi

10.3109/10428194.2012.742525

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

1177-82

issue

6

eissn

1042-8194

issn

1029-2403

journal_volume

54

pub_type

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