Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia

Infant T-cell acute lymphoblastic leukaemia (iT-ALL) is a very rare and poorly defined entity with a poor prognosis. We assembled a unique series of 13 infants with T-ALL, which allowed us to identify genotypic abnormalities and to investigate prenatal origins. Matched samples (diagnosis/remission) were analysed by single nucleotide polymorphism-array to identify genomic losses and gains. In three cases, we identified a recurrent somatic deletion on chromosome 3. These losses result in the complete deletion of MLF1 and have not previously been described in T-ALL. We observed two cases with an 11p13 deletion (LMO2-related), one of which also harboured a deletion of RB1. Another case presented a large 11q14·1-11q23·2 deletion that included ATM and only five patients (38%) showed deletions of CDKN2A/B. Four cases showed NOTCH1 mutations; in one case FBXW7 was the sole mutation and three cases showed alterations in PTEN. KMT2A rearrangements (KMT2A-r) were detected in three out of 13 cases. For three patients, mutations and copy number alterations (including deletion of PTEN) could be backtracked to birth using neonatal blood spot DNA, demonstrating an in utero origin. Overall, our data indicates that iT-ALL has a diverse but distinctive profile of genotypic abnormalities when compared to T-ALL in older children and adults

Cicatrisation et pansements (conseil officinal)

Quelle que soit leur gravité, la guérison de plaies aiguës ou chroniques sera spontanée ou fera appel à la cicatrisation dirigée. La cicatrisation, mécanisme complexe, comprend plusieurs phases. Les nouvelles technologies de pansements tentent de s'adapter à chacune d'entre elles. " A chaque plaie son pansement " La pertinence de la cicatrisation en milieu humide, qui date des années soixante, a ouvert la voie au développement des pansements modernes conçus sur ce principe. La multiplicité des pansements actuels peut dérouter : hydrocolloïdes, hydrocellulaires, alginates, films semi-perméables, interfaces... Ce travail permettra de mieux les distinguer. Les difficultés et les erreurs dans la mise en œuvre du traitement sont dues à une mauvaise connaissance des techniques de soins qui ont évolué. En effet les plaies doivent être lavées avec un savon doux, de l'eau ou du sérum physiologique. les antibiotiques et les antiseptiques nocifs pour les cellules en croissance doivent être utilisés à bon escient. Le renouvellement du pansement est effectué que si celui-ci se décolle spontanément (à saturation) etc. A l'heure actuelle, les études se poursuivent dans le domaine des facteurs de croissance (FC) issus pour la plupart des progrès du génie génétique. De nouvelles formes de pansements associant plusieurs matériaux et principes actifs sont au cœur des travaux de recherches orientés pour franchir une nouvelle étape vers une cicatrisation plus rapide.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Mise au point d'une technique de dosage génique par PCR en temps réel pour la détection des délétions chromosomiques 9p21 dans les leucémies aiguës lymphoblastiques de l'enfant

PARIS-BIUP (751062107) / SudocSudocFranceF

Suivi de la maladie résiduelle dans les leucémies aiguës lymphoblastiques avec réarrangement du gène MLL

PARIS-BIUP (751062107) / SudocSudocFranceF

Aspects cliniques, génétiques, cellulaires et sensibilité in vitro aux drogues dans la leucémie myélomonocytaire juvénile

CAEN-BU Médecine pharmacie (141182102) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

PReS-FINAL-2353: Are rasopathies new monogenic predisposing conditions to the development of systemic lupus erythematosus?

International audienc

Overexpression of CEBPA resulting from the translocation t(14;19)(q32;q13) of human precursor B acute lymphoblastic leukemia

Subtle variation in the expression or function of a small group of transcription factors can drive leukemogenesis. The CEBPA protein is known to regulate the balance between cell proliferation and differentiation during early hematopoietic development and myeloid differentiation. In human myeloid leukemia, CEBPA is frequently inactivated by mutation and indirect and posttranslational mechanisms, in keeping with tumor suppressor properties. We report that CEBPA is activated by juxtaposition to the immunoglobulin gene enhancer upon its rearrangement with the immunoglobulin heavy-chain locus in precursor B-cell acute lymphoblastic leukemia harboring t(14;19)(q32;q13). Overexpression of apparently normal CEBPA RNA or protein was observed in 6 patients. These data indicate that CEBPA may exhibit oncogenic as well as tumor suppressor properties in human leukemogenesis.<br/

Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients.

Heterozygous germline mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome

Variants of SOS2 are a rare cause of Noonan syndrome with particular predisposition for lymphatic complications

International audienc