B-RAF and another Hit

In NEJM today an Italian team did a splendid piece of genetic investigative work finding B-RAF changes identical to that in the melanoma work in Hairy Cell Leukemia patients. Cancer Research in the UK has a good summary as well.

The article states:

In 30 of the 48 patients with the V600E variant (including the index patient), the high purity of leukemic cells (>90%) allowed for the analysis of the zygosity of the mutation without substantial interference of wild-type alleles contributed by contaminating nonleukemic cells. In 26 of these 30 patients, the mutation appeared as a double peak...

 The V600E mutation results in the constitutive activation of BRAF kinase activity. Therefore, we assessed the phosphorylation status of MEK (the immediate downstream kinase target of BRAF) and ERK (the kinase phosphorylated by active MEK), using antibodies that specifically recognize phosphorylated MEK and ERK.

The similarity to the melanoma case is quite interesting. They conclude:

BRAF V600E was present in all 48 patients with HCL in our study. However, given the relatively small number of patients who were evaluated, we cannot rule out the possibility that some patients with HCL may not carry the BRAF V600E mutation. It must also be stressed that all samples that were analyzed in this study contained at least 30% neoplastic cells, which was the threshold for detecting a heterozygous clonal mutation by direct Sanger sequencing in our study. The detection of BRAF V600E in HCL samples containing lower proportions of leukemic cells will require more sensitive molecular techniques. If antibodies against the BRAF V600E variant protein become available, immunohistochemical analysis may be an alternative approach.