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Hairy cell leukemia (LT) accounts for 2% of all leukemias. The diagnosis is based on the presence in the blood and/or the marrow of hairy cells expressing CD103, CD123, CD11c and CD25. The BRAFV600E mutation, a molecular marker of the disease, is present in more than 80% of cases. LT should be distinguished from other chronic B-cell lymphoproliferative disorders, including the variant form of hairy cell leukemia (HCL-V) and diffuse splenic red pulp lymphoma (DSRPL). Progress has recently been made in the management of patients. The purine analogues (PNAs) in monotherapy, deoxycoformycin (DCF) or 2-chloro-deoxyadenosine (CDA), remain the first-line reference treatment. PNAs can be associated with anti-CD20 monoclonal antibodies (rituximab, obinutuzumab) and are now being introduced from the first line, with immunochemotherapy making it possible to obtain prolonged complete remissions (CR). In patients with relapsed/refractory (R/R) hairy cell leukemia, new therapeutic options emerged: immunotoxins, BRAF (BRAFi) or BTK inhibitors. The different options have to be discussed in a multidisciplinary consultation meeting. In patients with HCL-V, immunochemotherapy is the first-line standard of treatment. In all cases, prolonged haematological monitoring is necessary, because of the increased risk of secondary cancer, particularly the risk of hematologic malignancies. [ABSTRACT FROM AUTHOR]

Résumé: La leucémie à tricholeucocytes (HCL) est une hémopathie lymphoïde B mature rare, à cellules chevelues, caractérisée par la présence de la mutation BRAF V600E . Dans la forme variante (HCL-v), la mutation BRAF V600E est absente mais des mutations du gène MAP2K1 sont observées dans un tiers des cas. Ces mutations entraînent une activation constitutive de la voie des MAP-kinases. Le développement des techniques de séquençage à haut débit permet de mieux définir le paysage mutationnel de la HCL et de la HCL-v. Dans la HCL, des mutations récurrentes de CDKN1B (13 %) et de KLF2 (9,5 %) sont souvent identifiées et associées à BRAF V600E . CDKN1B code la protéine p27 impliquée dans la régulation du cycle cellulaire et KFL2 un régulateur négatif de la voie NF-κB. Dans la HCL-v, les mutations les plus fréquemment identifiées sont les mutations de MAP2K1 (42 %), de TP53 (26,5 %), de U2AF1 (16 %) et de KDM6A (16 %). U2AF1 code un composant du spliceosome et KDM6A , une lysine déméthylase. Dans la HCL et la HCL-v, de nombreuses mutations impliquent les gènes impliqués dans la régulation épigénétique, notamment KMT2C (MLL3), KDM6A (UTX), ARID1A , ARID1B , CREBBP et EZH2. L'identification du profil de mutations dans les proliférations à cellules chevelues pourrait permettre d'envisager, notamment dans les formes réfractaires de HCL ou de HCL-v, un traitement personnalisé. Hairy cell leukemia (HCL) is a rare mature B-cell chronic lymphoproliferative disorder, characterized by the identification of the BRAF V600E mutation. In the variant form (HCL-v), the BRAF V600E mutation is absent, but mutations of the MAP2K1 gene are observed in a third of the cases. These mutations lead to a constitutive activation of the MAP-kinase pathway. The development of high-throughput sequencing techniques makes it possible to better define the mutational landscape of HCL and HCL-v. In HCL, recurrent mutations of CDKN1B (13%) and KLF2 (9.5%) are often identified and associated with BRAF V600E . CDKN1B codes for the p27 protein involved in cell cycle regulation and KFL2 for a negative regulator of the NF-κB pathway. In HCL-v, the mutations most frequently identified are MAP2K1 (42%), TP53 (26.5%), U2AF1 (16%) and KDM6A (16%) mutations. U2AF1 encodes a spliceosome component and KDM6A , for a lysine demethylase. In HCL and HCL-v, many mutations involve genes involved in epigenetic regulation, including KMT2C (MLL3), KDM6A (UTX), ARID1A , ARID1B , CREBBP , and EZH2. The identification of the mutations profile in the hairy cells proliferative disorders makes it possible to adapt a personalized treatment, particularly in the refractory forms of HCL or HCL-v. [ABSTRACT FROM AUTHOR]

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Copyright of IBS, Immuno-analyse & Biologie Specialisee is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé: La leucémie à tricholeucocytes est un syndrome lymphoprolifératif B chronique rare de l’adulte évoqué devant une splénomégalie, une pancytopénie et une diminution caractéristique des monocytes. Le diagnostic est confirmé devant la présence dans le sang ou la moelle de cellules à « cheveux » CD19+ CD20+ CD25+ CD11c+. La leucémie à tricholeucocytes est dans de rares cas révélée par des arthrites. Ces atteintes articulaires sont rapportées soit à la leucémie à tricholeucocytes, soit à des pathologies dysimmunitaire. C’est ainsi que la polyarthrite rhumatoïde réalise parfois des tableaux polymorphes susceptibles d’égarer le diagnostic. La monocytopénie est un élément fondamental d’orientation. La découverte de cellules tricholeucocytaires dans le liquide articulaire confirme l’arthrite leucémique. Le traitement repose sur les analogues des purines. L’un des principaux diagnostics différentiels est le syndrome de Felty associant polyarthrite rhumatoïde, neutropénie et splénomégalie et correspondant le plus souvent à un syndrome lymphoprolifératif T. Nous rapportons sur une série de 27 cas, un cas de leucémie à tricholeucocytes révélé par des manifestations articulaires. [Copyright &y& Elsevier]

Fifteen spleens with hairy cell leukemia are studied with immunofluorescent (7 cases), electron microscopic (5 cases), and usual histologic methods. The findings are: enlargment of the spleen (weight always superior to 400 g), diffuse red pulp infiltration by ambiguous cells with regular repartition of nuclei and clear spaces between them, hairy aspects of the cytoplasmic membrane which are especially observed on semi-thin and ultra-thin sections, presence of particular cytoplasmic inclusion bodies (polysome lamellae complex). The cellular infiltration is accompanied by some vascular modifications: pseudo angiomatosis lesions, nodular formations ressembling splenomas. An important hypertrophy of the splenic macrophages with erythrophagocytosis and siderosis is also observed. These two phenomena partly explain the anemia. [ABSTRACT FROM AUTHOR]

Hairy cell leukemia is a rare form of leukemia: three hundred new cases are diagnosed each year in France. The diagnosis is based on: (1) morphological examination of the blood and bone marrow smear, (2) analysis by flow cytometry of hairy cells, which express three or the four following markers: CD11c, CD25, CD103 and CD123, (3) identification of the BRAF V600E mutation, a true molecular marker of the disease. The management of treatment has evolved considerably in recent years. As of today, the purine analogues remain the standard treatment in the first line. Relapses are however observed in about 40% of cases. In the event of a first relapse, the preferred option is treatment with immunochemotherapy i.e. a combination of cladribine plus rituximab. Subsequent relapses are treated with moxetumomab pasudotox or BRAF inhibitors which provide indisputable benefits if third-line treatment is required. We will discuss in patients with relapsed/refractory hairy cell leukemia the needs for personalized medicine and the advantages and disadvantages of each treatment modality. The good prognosis for LT requires treatments that are not immunosuppressive, non-myelotoxic, and do not increase the risk of secondary cancers., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

The standardized blood smear examination is the first step in the diagnosis of a B-cell chronic lymphoproliferative disorder and can guide further investigations. In the laboratory, the identification of hairy cells on blood smear is a matter of daily practice. Hairy cell proliferations represent heterogeneous entities and their respective diagnoses can be difficult. If hairy cell leukemia (HCL) and splenic marginal zone lymphoma (SMZL) represent separate entities, the variant form of HCL (HCLv) and splenic diffuse red pulp small B-cell lymphoma (SDRPL) remain provisional entities in the 2008 WHO classification. We discuss the main clinical and biological characteristics of these four entities and appropriate means to characterize, identify and distinguish from each other; standardized blood smear examination, multiparameter flow cytometry analysis, analysis of the repertoire of immunoglobulins heavy chains genes and their mutational status (mutated or unmutated profile), molecular analyses: BRAF gene V600E mutation in HCL and MAP2K1 gene mutations in HCLv. We also discuss the main therapeutic aspects with emphasis on the new targeted drugs that enter into force in the therapeutic arsenal.

Abstract: Background.: -IFN alpha are cytokines used for a number of years in the treatment of certain hemopathies, ie. of a myeloid and lymphoid etiology. IFN alpha are a family of polypeptides produced by eukaryote cells in response to various stimulant agents. The first trials using this cytokine in humans were carried out by H. Strander in the years 1965-1970. IFN alpha contain anti-viral, anti-proliferative and immunomodulatory properties. The access of clinicians to IFN alpha molecules, in addition to elements produced by genetic engineering for approximately the past 20 years, has permitted a number of therapeutic trials to be carried out. In hematology the clinical interest of IFN alpha was primarily in chronic myeloid and lymphoid proliferating syndromes. Certain indications have to date been well demonstrated. However, the impact of IFN alpha on therapeutic care of certain hemopathies as compared to conventional treatment remains controversial. At the same time, the frequency of side effects from treatment with IFN alpha and its cost should be taken into consideration. Current position and major points.: -The therapeutic trials carried out over the past ten years have proven the interest of IFN alpha in, essentially, two diseases: on one hand chronic myeloid leukemia with the acquisition of cytogenetic remission and on the other malignant non-Hodgkin''s follicular type lymphoma. However, as regards other hemopathies the place of IFN alpha remains debatable. Perspectives.: -The future of IFN alpha use in the treatment of hemopathies appears to be linked to its association with new treatments,an association, however, where its efficacy and superiority should be demonstrated. This is the case in chronic myeloid leukemia where IFN alpha could be associated with aracytine or the inhibitors of tyrosine kinase. Also, in the treatment of malignant non-Hodgkin''s lymphomas as well as the studies concerning the association between IFN alpha and monoclonal antibodies, in particular antibody anti-CD 20. [Copyright &y& Elsevier]

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.