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BRAF mutations in acute leukemias

Leukemia volume 18, pages 170–172 (2004)Cite this article

TO THE EDITOR

When cells are stimulated by growth factor or other receptor–ligand interactions, RAS proteins become activated by exchanging GDP for GTP. The activated RAS, in turn, excite the mitogen-activated protein (MAP) kinase pathway (RAS-RAF-MEK-ERK-MAP kinase pathway) by recruiting the cytosolic protein RAF.1 The RAS-RAF-MEK-ERK-MAP kinase pathway plays a critical role in cell proliferation, and is frequently activated in cancer cells. For example, approximately 10–20% of all human tumors contain mutated versions of RAS proteins, which activate the downstream pathway.1 Recently, Davies et al2 identified somatic mutations of BRAF, one of the RAF members, in 66% of malignant melanomas and at a lower frequency in a wide range of human cancers. So far, all BRAF mutations have been reported within two kinase domains, and the most common mutation is a single substitution, V599E.2 Mutated BRAF proteins have elevated kinase activity and transforming activity in NIH3T3 cells.2 Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation.2 In leukemias, the RAS-RAF-MEK-ERK-MAP kinase pathway is known to be frequently activated, and the NRAS mutation is partly responsible for this activation.3 BRAF is well expressed in hematopoietic cells,4 and expression of activated BRAF can relieve the cytokine dependence and can result in the transformation of hematopoietic cells.4,5,6 To date, there is only one report on BRAF mutation in leukemia samples, which detected no BRAF mutations in acute myelogenous leukemia (AML) FAB type M1 and M2 from the United Kingdom.7 Because it is possible that other types of acute leukemia or other racial populations with acute leukemia might harbor the BRAF mutation, we investigated the occurrence of BRAF gene mutations in acute leukemias in the Korean adult population.

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Acknowledgements

This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea. (02-PJ1-PG10-20801-0004).

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Authors and Affiliations

  1. Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea

    J W Lee, Y H Soung, W S Park, S Y Kim, S W Nam, J Y Lee, N J Yoo & S H Lee

  2. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

    W S Min

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Lee, J., Soung, Y., Park, W. et al. BRAF mutations in acute leukemias. Leukemia 18, 170–172 (2004). https://doi.org/10.1038/sj.leu.2403201

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