@article{Enrico Tiacci_Gianluca Schiavoni_Maria Paola Martelli_Emanuela Boveri_Roberta Pacini_Alessia Tabarrini_Silvia Zibellini_Alessia Santi_Valentina Pettirossi_Elisabetta Fortini_Stefano Ascani_Luca Arcaini_Giorgio Inghirami_Marco Paulli_Brunangelo Falini_2013, place={Pavia, Italy}, title={Constant activation of the RAF-MEK-ERK pathway as a diagnostic and therapeutic target in hairy cell leukemia}, volume={98}, url={https://haematologica.org/article/view/6635}, DOI={10.3324/haematol.2012.078071}, abstractNote={The BRAF-V600E mutation defines genetically hairy cell leukemia among B-cell leukemias and lymphomas. In solid tumors, BRAF-V600E is known to aberrantly activate the oncogenic MEK-ERK pathway, and targeted BRAF and/or MEK inhibitors have shown remarkable efficacy in clinical trials in melanoma patients. However, the MEK-ERK pathway status in hairy cell leukemia has not been thoroughly investigated. We assessed phospho-ERK expression in 37 patients with hairy cell leukemia and 44 patients with neoplasms mimicking hairy cell leukemia (40 splenic marginal zone lymphoma, 2 hairy cell leukemia-variant and 2 splenic lymphoma/leukemia unclassifiable) using immunohistochemistry on routine biopsies and/or Western blotting on purified leukemic cells, and correlated the phospho-ERK status with the BRAF-V600E mutation status. Besides confirming the constant presence of BRAF-V600E in all patients with hairy cell leukemia, we observed ubiquitous phospho-ERK expression in this malignancy. Conversely, all 44 cases with neoplasms mimicking hairy cell leukemia were devoid of BRAF-V600E and none expressed phospho-ERK. Furthermore, the two exceptionally rare cases of non-hairy cell leukemia unclassifiable chronic B-cell neoplasms previously reported to be BRAF-V600E<sup>+</sup&gt; on allele-specific polymerase chain reaction lacked phospho-ERK expression as well, suggesting the presence of the mutation in only a small part of the leukemic clone in these cases. In conclusion, our findings support the use of phospho-ERK immunohistochemistry in the differential diagnosis between hairy cell leukemia and its mimics, and establish the MEK-ERK pathway as a rational therapeutic target in this malignancy.}, number={4}, journal={Haematologica}, author={Enrico Tiacci and Gianluca Schiavoni and Maria Paola Martelli and Emanuela Boveri and Roberta Pacini and Alessia Tabarrini and Silvia Zibellini and Alessia Santi and Valentina Pettirossi and Elisabetta Fortini and Stefano Ascani and Luca Arcaini and Giorgio Inghirami and Marco Paulli and Brunangelo Falini}, year={2013}, month={Mar.}, pages={635-639} }