Intérêt du Glivec® (mésylate d'imatinib) dans le traitement de la leucémie myéloïde chronique

La leucémie myéloide chronique (LMC) est une hémopathie maligne caractérisée par la présence du chromosome Philadelphie, porteur du gène Bcr-Abl, résultat d'une translocation génétique. Ce gène signe la maladie et entraîne la formation d'une protéine, une tyrosine kinase. Cette dernière agit au niveau des cellules souches de la moelle osseuse en perturbant les phénomènes de différenciation, d'adhésion cellulaire et inhibe le phénomène d'apoptose(mort cellulaire programmée). Il en résulte des perturbations hématologiques et cliniques, qui évoluent au cours de la maladie selon trois phases : une phase chronique, une phase d'accélération et une phase blastique, à l'issue fatale en quelques années. Les traitements jusqu'à aujourd'hui (chimiothérapie, interféron) n'ont permis que des rémissions temporaires, suivies de rechutes fatales pour le patient. La découverte de la tyrosine kinase qui est à l'origine de la LMC a permis de mettre au point des traitements spécifiques de la maladie, notamment le mésylate d'imatinib(Glivec®), qui agit directement au niveau de la tyrosine kinase. Ce traitement a permis en quelques années et à la suite de nombreux essais cliniques, de prouver son efficacité et sa supériorité par rapport aux traitements utilisés jusque là. Il semble malgré tout qu'un phénomène de résistance apparaisse parfois au début ou au cours du traitement. De plus, il subsiste une faible proportion de gène Bcr-Abl après traitement, c'est la maladie résiduelle. Même si l'allogreffe est le seul traitement curatif actuellement, l'imatinib reste néanmoins un traitement incontournable et laisse la porte ouverte à de nouveaux espoirs dans le traitement de la LMCAMIENS-BU Santé (800212102) / SudocSudocFranceF

Activated Stat Related Transcription Factors in Acute Leukemia

International audienceCell proliferation and differentiation are under the control of cytokines and growth factors. Different signaling pathways are involved in the transmission of a specific signal through successive phosphorylation and dephosphorylation of proteins leading to gene transcription necessary for growth and differentiation. The cytokines and growth factors activate the Stat family of transcription factors. The Jak-Stat pathway is essential for cytokine signal transduction. Dysregulation of this cascade might lead to uncontrolled hematopoiesis. Studies have been carried out to examine the functionality of this pathway in cells from patients with acute leukemia. Members of the Stat protein family (Stat1, Stat3 and Stat5) are constitutively activated in cells collected from some acute leukemias suggesting dysregulation of the Jak-Stat pathway. Evidence of the existence of constitutively activated spliced variants of Stat3 and Stat5 proteins are described. The mechanisms of such activation remain to be clarified

Toxoplasmose disséminée chez un patient sous methotrexate

A 60 years old patient treated by methotrexate and prednisolone for rheumatoid arthritis, was admitted at the hospital for pulmonary infection refractory to antibiotics. After a few days he was transferred to the intensive care unit for pancytopenia. Direct examination of bone marow revealed the presence of toxoplasma into polymorphonuclears and monocytes. However, in spite of a specific treatment the patient died two days later of disseminated toxoplasmosis

Rituximab therapy for hairy cell leukemia : a retrospective study of 41 cases

The purine analogs (PAs) cladribine and pentostatin have transformed the prognosis of hairy cell leukemia (HCL). However, some patients still relapse after PAs, or fail to reach an optimal response, and new agents are needed to further improve treatment outcome. We retrospectively studied 41 HCL patients from 10 centers in France and Belgium, who received 49 treatment courses with the anti-CD20 monoclonal antibody rituximab. Most of the patients were treated at relapse (84 % of cases) and rituximab was combined to a PA in 41 % of cases. Overall, response rate is 90 % including 71 % complete hematologic responses (CHRs). Frontline treatment, combination therapy, and absolute neutrophil count were associated with response in multivariate analysis. Three-year relapse-free and overall survivals are 68 and 90 %, respectively. When combined to a PA, rituximab yields a 100 % response rate, even beyond frontline therapy. In contrast, response rate is only 82 % (59 % CHR) when rituximab is used alone. In this latter setting, relapse rate is 56 % and median time to relapse is 17.5 months. All eight patients who were treated two times with the antibody responded again to retreatment. We confirm the high efficacy of the combination rituximab + PA. However, when rituximab is used as monotherapy, response rate is lower and the high relapse rate is a concern. Prospective clinical trials are needed to confirm the superiority of the combination rituximab + PA over PA alone, both as frontline therapy and at relapse

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

International audienceZAP-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

Evaluation of residual disease in b-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements

We evaluated minimal residual disease (MRD) in 23 CD5 + B-chronic lymphocytic leukemia (CLL) patients who achieved clinico-hematological remission confirmed by bone-marrow biopsy. MRD was evaluated by dual marker analysis flow-cytometry using CD5 and CD19 markers, and by the study of Ig heavy chain gene rearrangements using the fast polymerase chain reaction (PCR). According to our laboratory conditions patients were considered to be in complete phenotypic remission when total CD19 + cells were >25% and the ratio of CD5 + CD19 + /CD19 + cells was >25% According to these strict criteria only 9 of the 23 patients were in complete phenotypic remission. In order to evaluate the sensitivity of the above method, PCR analysis of the configuration of the Ig heavy chain gene region was performed in 12 of these patients. Five of 7 patients in complete phenotypic remission retained a detectable monoclonal rearrangement of the Ig heavy chain gene. For the remaining 5 patients in partial phenotypic remission, only one failed to show a monoclonal band and this is probably explained by the presence of an unusual gene rearrangement. In conclusion, this study suggests that PCR is more sensitive than dual marker flow-cytometry for evaluation of residual disease and that it is indeed possible to achieve complete remission at the molecular level, in B-CLL. Nevertheless, we suggest a word of caution as this was a retrospective study, and samples were not assessed before treatment. Thus the possibility that apparent molecular remission might correspond to unusual gene rearrangements cannot be completely excluded in these cases. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

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 patient’s case with rare phenotypic and genotypic characteristics is described with review of major clinical biological and therapeutic approaches in MCL

Anticiper les changements technologiques pour ne plus les subir

Carte blanche pour l'instauration en Wallonie d'un "Institut d'évaluation des technologies" : allons-nous encore nous contenter de subir les développements technologiques ou allons-nous choisir de les débattre, les questionner et participer de manière concertée à orienter leur trajectoire