Jean-François Claisse

Thalidomide in advanced mastocytosis

Mastocytosis is an acquired orphan disease characterized by the abnormal accumulation of mast cells responsible for organ failure and systemic symptoms. Cytoreductive drugs have been shown to be effective, but have rarely resulted in complete or long‐term remission. We report two patients with advanced systemic mastocytosis (SM) who were treated successfully with thalidomide, given at the maximal tolerated dosage. B and C‐findings as well as clinical symptoms rapidly improved. After a follow‐up of more than 1 year, the patients remained in partial remission. Thalidomide seems to be an active drug in advanced SM. However, clinical trials are warranted to define its efficacy and safety profiles.

Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive

Mast cell leukemia (MCL) is a rare and aggressive disease with poor prognosis and short survival time. D816V c-KIT mutation is the most frequent molecular abnormality and plays a crucial role in the pathogenesis and development of the disease. Thus, comprehensive diagnostic investigations and molecular studies should be carefully carried out to facilitate the therapeutic choice. A MCL patients case with rare phenotypic and genotypic characteristics is described with review of major clinical biological and therapeutic approaches in MCL.

Multi-drug resistance mediated by P-glycoprotein overexpression is not correlated with ZAP-70/CD38 expression in B-cell chronic lymphocytic leukemia

ZAP-70 and CD38 expression can identify B-cell chronic lymphocytic leukemia with an inferior clinical outcome. Many groups have investigated the meaning of the expression of these two proteins and the correlation with the bad prognosis in B-CLL. But nobody has investigated the relation between the multidrug resistance mediated by Pgp overexpression (MDR1) and ZAP-70/CD38 coexpression. Forty-one untreated and stage A patients, either ZAP-70+CD38+ or ZAP-70−CD38−, were tested to determine the MDR1 status. MDR1 was observed in 41% of CLL ZAP-70+CD38+ and in 37% of CLL ZAP-70−CD38−. The difference was not significant (p = 0.745). Patients with ZAP-70 and CD38 positive CLL can not be candidates for MDR1 antagonists.

Phorbol myristate acetate, but not CD40L, induces the differentiation of CLL B cells into Ab-secreting cells

In this study, we investigated the capacity of chronic lymphocytic leukemia (CLL) B cells to undergo terminal differentiation into Ig‐secreting plasma cells in T cell‐independent and T cell‐dependent responses. We used a two‐step model involving stimulation with phorbol myristate acetate (PMA) and CD40L, together with cytokines (PMA/c and CD40L/c), for 7 days. We describe immunophenotypic modifications, changes in the levels of mRNA and protein for transcription factors and morphological and functional events occurring during the differentiation of CLL B cells into antibody‐secreting cells (ASCs). The induction of differentiation differed significantly between the CD40L/c and PMA/c culture systems. The PMA/c culture system allowed CLL B cells to differentiate into IgM‐secreting cells with an immunophenotype and molecular profile resembling those of preplasmablasts. By contrast, CD40L/c‐stimulated cells had a phenotype and morphology similar to those of activated B cells and resembling those of the CLL B cells residing in the lymph node and bone marrow. These data suggest that the CLL B cells are not frozen permanently at a stage of differentiation and are able to differentiate into ASCs as appropriate stimulation are provided. The data presented here raise questions about the molecular processes and stimulation required for CLL B‐cell differentiation and about the inability of CD40 ligand to induce differentiation of the CLL B cells.

Predictive significance of smudge cell on routine blood smear in lymphocytosis

Une hyperlymphocytose se definit par une augmentation du nombre absolu de lymphocytes sanguins superieur a 4 × 109/L chez l’adulte. Les etiologies sont differentes en fonction de sa duree (transitoire ou chronique), de l’âge du patient et de la morphologie lymphoide. En pratique clinique et biologique quotidienne, la caracterisation de ces trois criteres est un prealable indispensable afin de [...]

Acute Promyelocytic Leukemia with Atypical Cytologic Features

view of the histologic diagnosis of pure SCC, clinical examinations, including cervical smear, esophagogram, laryngogram, chest radiography and ultrasound scan of the abdomen, excluded a metastatic SCC. The diagnosis of primary SCC of the breast is to be made on cytology, if the malignant squamous component constitutes > 90% of the tumor cell area. Moreover, pure SCC cells do not form tubules, papillae or cell clusters with common borders, which were not seen in our case.4 The histogenesis of this tumor is not clear. Some authors believe that it arises as a result of metaplastic process due to the influence of female hormones (estrogen and progesterone)5 and insulin6 or may also arise many years after implantation of silicone prostheses.7 In summary, one has to pay attention to the highpower cytologic details and background cellular components for a possible preoperative diagnosis of SCC, but one needs an extensive sampling of the tumor histologically for the diagnosis of pure SCC.