Mastocytosis in mice expressing human Kit receptor with the activating Asp816Val mutation

Mastocytosis is a rare neoplastic disease characterized by a pathologic accumulation of tissue mast cells (MCs). Mastocytosis is often associated with a somatic point mutation in the Kit protooncogene leading to an Asp/Val substitution at position 816 in the kinase domain of this receptor. The contribution of this mutation to mastocytosis development remains unclear. In addition, the clinical heterogeneity presented by mastocytosis patients carrying the same mutation is unexplained. We report that a disease with striking similarities to human mastocytosis develops spontaneously in transgenic mice expressing the human Asp816Val mutant Kit protooncogene specifically in MCs. This disease is characterized by clinical signs ranging from a localized and indolent MC hyperplasia to an invasive MC tumor. In addition, bone marrow–derived MCs from transgenic animals can be maintained in culture for >24 mo and acquire growth factor independency for proliferation. These results demonstrate a causal link in vivo between the Asp816Val Kit mutation and MC neoplasia and suggest a basis for the clinical heterogeneity of human mastocytosis

Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation

Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR-125b was able to interfere with primary human CD34+ cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2;11) translocation define a new clinicopathological entity

Les lymphomes B ALK positifs (une nouvelle entité parmi les lymphomes B diffus à grandes cellules)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Émergence d’une spécialité médicale nouvelle : la pathologie

Cet article a pour objectif de positionner l’anatomie pathologique dans la révolution qui tente de faire progressivement de la médecine une science. Plusieurs aspects de cette discipline stratégique seront abordés. Nous essaierons de montrer quels sont les enjeux de son évolution en pathologie inflammatoire et surtout oncologique

Les proliférations lymphoïdes cutanées CD 30 positives (étude anatomo-clinique à partir de 38 cas)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Contribution à l'étude de la translocation t(14 ; 18) dans les lymphomes folliculaires (intérêt des sondes clonospécifiques dans la direction de la maladie résiduelle)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Implication du virus d'Epstein-Barr dans la maladie de Hodgkin-classique (rôle du polymorphisme du gène viral LMP-1-BNLF1 sur les propriétés oncogéniques de la protéine LMP-1)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Etude des délétions géniques d'ATM (ataxia-telangectasia mutated) et de p53 dans les cellules de Reed-Sternberg dans la maladie de Hodgkin par technique de PCR sur cellules isolées par micromanipulation "single cell PCR

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF