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Hairy cell leukemia is a rare chronic lymphoproliferative disorder. Its diagnosis remains difficult due to different variant forms and differential diagnosis that are splenic marginal zone lymphoma and b-prolymphocytic leukemia. The prognosis of this malignancy has been transformed by purine nucleoside analogs, interferon, monoclonal antibodies and recombinant immunotoxins usually used in refractory or relapsed disease. The discovery of BRAF V600E mutation has become the milestone in the disease's history since it was uniformly identified in a HCL series in 2011. This mutation, commonly identified in melanoma, involves the protooncogene BRAF, a MAP3Kinase belonging to the RAF-MEK-ERK signaling pathway, which is the central key in several oncogenic processes. This mutation suggests disease-specific oncogene dependence. The detection of this mutation provides an additional diagnosis marker (because not found in variant forms), a best for monitoring minimal residual disease and a therapeutic target with the BRAF inhibitors in specific subgroups of patients, already tested in melanoma. This review aims to summarize the clinical and biological aspects and treatment of hairy cell leukemia and discusses the perspectives provided by the discovery of BRAF mutation in this disease.

Mammalian target of rapamycyin (mTOR) is a downstream serine/threonine kinase of the PI3K/AKT pathway that integrates signals from the microenvironment such as cytokines, growth factors, and nutriments to regulate multiple cellular processes, including mRNA translation, autophagy, metabolism, growth and survival. mTOR operates in two distinct multi-protein complexes: mTORC1 and mTORC2; sharing mTOR kinase as a common catalytic subunit, mTORC1 controls cell growth and mTORC2 modulates cell survival and drug resistance. mTOR signalling pathway has been found to be deregulated in many haematological malignancies, and has been designed as an attractive anti-tumor target. Thereby, mTOR inhibition with rapamycin (sirolimus) or its derivates (rapalogs) represents promising treatments, either alone or in combination with strategies to target other pathways that may overcome resistance. At present time, numerous clinical trials with mTOR inhibitors are ongoing for treatment of haematological diseases with modest or promising results. The aim of this review is to present the rationale for using mTOR inhibitors in haematology, first via biological explanations and secondly, by focusing on each haematological malignancies with new perspective of treatment.

Hairy cell leukemia is a rare chronic lymphoproliferative disorder. Its diagnosis remains difficult due to different variant forms and differential diagnosis that are splenic marginal zone lymphoma and b-prolymphocytic leukemia. The prognosis of this malignancy has been transformed by purine nucleoside analogs, interferon, monoclonal antibodies and recombinant immunotoxins usually used in refractory or relapsed disease. The discovery of BRAF V600E mutation has become the milestone in the disease's history since it was uniformly identified in a HCL series in 2011. This mutation, commonly identified in melanoma, involves the protooncogene BRAF, a MAP3Kinase belonging to the RAF-MEK-ERK signaling pathway, which is the central key in several oncogenic processes. This mutation suggests disease-specific oncogene dependence. The detection of this mutation provides an additional diagnosis marker (because not found in variant forms), a best for monitoring minimal residual disease and a therapeutic target with the BRAF inhibitors in specific subgroups of patients, already tested in melanoma. This review aims to summarize the clinical and biological aspects and treatment of hairy cell leukemia and discusses the perspectives provided by the discovery of BRAF mutation in this disease.

Mammalian target of rapamycyin (mTOR) is a downstream serine/threonine kinase of the PI3K/AKT pathway that integrates signals from the microenvironment such as cytokines, growth factors, and nutriments to regulate multiple cellular processes, including mRNA translation, autophagy, metabolism, growth and survival. mTOR operates in two distinct multi-protein complexes: mTORC1 and mTORC2; sharing mTOR kinase as a common catalytic subunit, mTORC1 controls cell growth and mTORC2 modulates cell survival and drug resistance. mTOR signalling pathway has been found to be deregulated in many haematological malignancies, and has been designed as an attractive anti-tumor target. Thereby, mTOR inhibition with rapamycin (sirolimus) or its derivates (rapalogs) represents promising treatments, either alone or in combination with strategies to target other pathways that may overcome resistance. At present time, numerous clinical trials with mTOR inhibitors are ongoing for treatment of haematological diseases with modest or promising results. The aim of this review is to present the rationale for using mTOR inhibitors in haematology, first via biological explanations and secondly, by focusing on each haematological malignancies with new perspective of treatment.