Analytical validation of the Liaison hGH assay (DiaSorin)

peer reviewe

Monoclonal B-cell lymphocytosis: asymptomatic condition or pretumoral stage

peer reviewe

Etude des mécanismes requis pour le potentiel oncogénique de BCL-3 par l'intermédiaire d'études d'interactome.

The oncogenic protein BCL-3, a member of the Iκ;B family, was originally identified in a subset of human B-cell chronic lymphocytic leukemias that carry a translocation t(14,19), which results in BCL-3 overexpression. BCL-3 is also overexpressed in many solid tumors, such as in breast cancers and in cylindromas. This Iκ;B protein activates or represses gene transcription through binding with the NF-κ;B proteins p50 and p52. Furthermore, BCL-3 is K63-linked polyubiquitinated, which leads to its translocation into the nucleus and to its target genes expression. BCL-3 is also K48-linked polyubiquitinated after GSK3 phosphorylation, which leads to its subsequent proteasomal degradation. However, the mechanisms underlying both its polyubiquitination and its ability to repress gene transcription remain poorly understood. In order to gain more insight into these BCL-3 functions, parallel screenings involving both yeast-two-hybrid experiments and biochemical purifications led to the identification of BCL-3-interacting partners. Those screenings identified CtBP as a molecule required for the ability of BCL-3 to repress gene transcription. CtBP is also required for the stability, for the oncogenic potential and for the ability of BCL-3 to inhibit UV-mediated cell apoptosis in keratinocytes. We also defined the E3 ligase TBLR1 as a key element involved in BCL-3 polyubiquitination and degradation through a GSK3-independent pathway and the proteasome subunit PSMB1 as a protein required for the GSK3-dependent and -independent proteasomal degradation of polyubiquitinated BCL-3. Importantly, all interactions require unique motifs within the amino-terminal domain of BCL-3.In conclusion, our data define multiple BCL-3-associated proteins that differentially and specifically regulate its function and stability and indicate that a better understanding of the mechanisms underlying the oncogenic properties of this Iκ;B protein could be achieved through similar interactomic studies

Contribution of hematology analyzers (Sysmex XN-Series) in the rapid diagnosis of malaria : case reports

peer reviewedLe paludisme est une maladie potentiellement sévère sévissant particulièrement en Afrique. En Europe, les cas de paludisme proviennent majoritairement de voyageurs revenant de zones endémiques. La symptomatologie non spécifique peut ne pas alerter le clinicien si cette notion de voyage n’est pas abordée. Or, le diagnostic et l’instauration rapide d’un traitement empêchent l’évolution vers les formes graves, notamment en cas d’infection à Plasmodium falciparum, capable d’engager le pronostic vital en 24h. La microscopie sur frottis mince et en goutte épaisse est la méthode de référence pour le diagnostic mais certains automates d’hématologie ont démontré leur capacité à participer au diagnostic précoce. Nous décrivons deux cas illustrant la contribution de la chaine automatisée Sysmex XN-9100 dans le diagnostic de la malaria. Le premier cas clinique est celui d’un jeune homme infecté par de nombreux gamétocytes de Plasmodium falciparum. Ceux-ci forment une population additionnelle visualisable sur les scattergrammes des leucocytes WNR (numération des leucocytes) et WDF (formule leucocytaire). Le second cas concerne un homme atteint de neuropaludisme, avec une parasitémie élevée à Plasmodium falciparum. Les hématies parasitées forment une discrète double population sur le scattergramme des réticulocytes, située à la limite de discrimination des globules rouges matures et des réticulocytes. Les anomalies des scattergrammes, visualisables en quelques minutes, offre une anticipation du diagnostic de malaria en comparaison à la microscopie sur frottis mince et goutte épaisse, technique nécessitant un temps et une expertise non négligeable

Blood, urine, and hair kinetic analysis following an acute lead intoxication

A case of lead exposure resulting from the accidental ingestion of a lead-containing solution is reported. Because of clinical management rapidly performed through chelation therapy by 2,3-dimercaptopropane sulfonate sodium and meso-2,3-dimercaptosuccinic acid, blood lead levels of this 51-year-old patient were moderate (412.9 μg/L) and no clinical symptoms were observed. Numerous blood and urine samples were collected for kinetic analysis of lead elimination. However, we report the first case in which hair samples were analyzed to determine the excretion level of lead after acute intoxication

Monoclonal B-cell lymphocytosis: from literature to laboratory practice

Monoclonal B-cell lymphocytosis (MBL) is defined as an asymptomatic condition characterized by the presence of less than 5,000 monoclonal B-cells per microliter and the absence of clinical signs or symptoms of a B-cell lymphoproliferative disorder. Most MBL cases involve B cells presenting an identical phenotype to CLL (CLL-like MBL) with a Catovsky-Matutes score of 3 to 5 and share the same chromosomal abnormalities than CLL. Depending on the absolute B cell count, one may distinguish low-count CLL-like MBL (500 B cells/muL) have a 1% to 2% per year risk of progression to CLL requiring therapy, a higher risk of infectious complications and mortality implicating an annual follow-up by hematologist. MBL may also express other less common phenotypes and are named atypical MBL in case of CD5 antigen expression (Catovsky-Matutes score: 1-2) and non-CLL-like MBL for CD5 negative cases (Catovsky-Matutes score: 0-2). Their poorer prognosis implicates imaging studies, bone marrow biopsy and cytogenetic analysis in addition to physical examination in order to rule out non-hodgkinien lymphoma, and require a more frequent follow-up. This review focuses on key concepts in the classification, diagnosis, monitoring and biology of MBL in laboratory practice