A multiparametric niche-like drug screening platform in acute myeloid leukemia.

Functional precision medicine in AML often relies on short-term in vitro drug sensitivity screening (DSS) of primary patient cells in standard culture conditions. We designed a niche-like DSS assay combining physiologic hypoxia (O2 3%) and mesenchymal stromal cell (MSC) co-culture with multiparameter flow cytometry to enumerate lymphocytes and differentiating (CD11/CD14/CD15+) or leukemic stem cell (LSC)-enriched (GPR56+) cells within the leukemic bulk. After functional validation of GPR56 expression as a surrogate for LSC enrichment, the assay identified three patterns of response, including cytotoxicity on blasts sparing LSCs, induction of differentiation, and selective impairment of LSCs. We refined our niche-like culture by including plasma-like amino-acid and cytokine concentrations identified by targeted metabolomics and proteomics of primary AML bone marrow plasma samples. Systematic interrogation revealed distinct contributions of each niche-like component to leukemic outgrowth and drug response. Short-term niche-like culture preserved clonal architecture and transcriptional states of primary leukemic cells. In a cohort of 45 AML samples enriched for NPM1c AML, the niche-like multiparametric assay could predict morphologically (p = 0.02) and molecular (NPM1c MRD, p = 0.04) response to anthracycline-cytarabine induction chemotherapy. In this cohort, a 23-drug screen nominated ruxolitinib as a sensitizer to anthracycline-cytarabine. This finding was validated in an NPM1c PDX model.

[Red blood cell alloimmunization among polytransfused patients in the National Hospital and University Center of Cotonou: about 51 cases]. / Allo-immunisation anti-érythrocytaire chez les polytransfusés au Centre National Hospitalier Universitaire de Cotonou: à propos de 51 cas.

Blood transfusion is a medical procedure used to treat patients with labile blood product. Each transfusion of globular concentrate exposes recipients to the risk of red blood cell alloimmunization. The test for red cell antibodies (RCA) ensures the immunohaematological safety of transfused patients. In Benin, this test is not performed in a systematic way or included either in the pre-transfusion or in the post-transfusion tests. The purpose of this study is to determine the presence of red cell antibodies among polytransfused patients. RCA was performed using indirect antiglobulin test on gel-filtration in 51 polytransfused patients including 26 selected in the Department of Hematology and 25 in the Department of Nephrology at the National Hospital and University Center of Cotonou. After phenotyping alloimmunized patients, tests for detecting signs of hemolysis were performed. Clinical data as well as those on transfusion were collected from transfusion registries and medical records. The prevalence of alloimmunization in our study population was 13.73%. The antibodies identified had the following characteristics: association of anti-RH1 and anti-RH3, anti LE1, association of anti-RH3 and anti-FY1. Alloantibodies were more frequent in patients who had received more than 15 packed red blood cells. Laboratory tests showed signs of hemolysis in one alloimmunized patient. There was no correlation between age, sex, clinical diagnosis and the occurrence of red blood cell alloimmunization. The test for red cell antibodies should be systematically performed in polytransfused patients in order to ensure better transfusion recipient safety in Benin.

L'expérience en cytologie hématologique au Bénin

Introduction : La maîtrise de la cytologie hématologique reste indispensable malgré l'avènement des automates. Objectif : Faire le point de la pratique de la cytologie hématologique au Bénin. Matériels et méthode : Etude transversale à visée descriptive et analytique comportant un volet ré-trospectif et un volet prospectif. Seize formations sanitaires tirées au hasard et réparties sur l'ensemble des 34 zones sanitaires que compte le pays avaient été incluses en tenant compte des différents niveaux de la pyramide sanitaire. Les données enregistrées ont été saisies avec Excel et analysées grâce au logiciel Epi info version 7.2. Résultats : Six hôpitaux sur 16 avaient un laboratoire d'Hématologie et seul le laboratoire d'Hématologie du Centre National Hospitalier Universitaire-HKM disposait de personnels spécialistes. Le nombre moyen de technicien était de 5 par centre et 60,4% d'entre eux étaient de niveau A. Le nombre moyen d'hémogrammes réalisés par mois était de 3000 pour le CNHU, 603 pour les Hôpitaux de zone et 549 pour les Centres Hospitaliers départementaux. L'étude du frottis sanguin était de réalisation systématique dans seulement 6 centres. Aucune autre activité de cytologie hématologique en dehors de l'hémogramme n'était réalisée sauf au CNHU-HKM et à l'Hôpital de zone de Tanguiéta qui réalisaient des myélogrammes et des adénogrammes. Ces deux derniers centres disposaient également d'un dispositif de télé-hémato-cytologie. Conclusion : Notre étude révèle des insuffisances en cytologie hématologique. Les solutions propo-sées passent par le recrutement et la formation de personnels qualifiés, l'équipement et l'approvisionnement des laboratoires