Five distinct biological processes and 14 differentially expressed genes characterize TEL/AML1-positive leukemia

<p>Abstract</p> <p>Background</p> <p>The t(12;21)(p13;q22) translocation is found in 20 to 25% of cases of childhood B-lineage acute lymphoblastic leukemia (B-ALL). This rearrangement results in the fusion of <it>ETV6 </it>(<it>TEL</it>) and <it>RUNX1 </it>(<it>AML1</it>) genes and defines a relatively uniform category, although only some patients suffer very late relapse. <it>TEL/AML1</it>-positive patients are thus an interesting subgroup to study, and such studies should elucidate the biological processes underlying TEL/AML1 pathogenesis. We report an analysis of gene expression in 60 children with B-lineage ALL using Agilent whole genome oligo-chips (44K-G4112A) and/or real time RT-PCR.</p> <p>Results</p> <p>We compared the leukemia cell gene expression profiles of 16 <it>TEL/AML1</it>-positive ALL patients to those of 44 <it>TEL/AML1</it>-negative patients, whose blast cells did not contain any additional recurrent translocation. Microarray analyses of 26 samples allowed the identification of genes differentially expressed between the TEL/AML1-positive and negative ALL groups. Gene enrichment analysis defined five enriched GO categories: cell differentiation, cell proliferation, apoptosis, cell motility and response to wounding, associated with 14 genes -<it>RUNX1, TCFL5, TNFRSF7, CBFA2T3</it>, <it>CD9</it>, <it>SCARB1, TP53INP1, ACVR1C, PIK3C3, EGFL7</it>, <it>SEMA6A, CTGF, LSP1, TFPI </it>– highlighting the biology of the <it>TEL/AML1 </it>sub-group. These results were first confirmed by the analysis of an additional microarray data-set (7 patient samples) and second by real-time RT-PCR quantification and clustering using an independent set (27 patient samples). Over-expression of <it>RUNX1 (AML1) </it>was further investigated and in one third of the patients correlated with cytogenetic findings.</p> <p>Conclusion</p> <p>Gene expression analyses of leukemia cells from 60 children with <it>TEL/AML1</it>-positive and -negative B-lineage ALL led to the identification of five biological processes, associated with 14 validated genes characterizing and highlighting the biology of the <it>TEL/AML1</it>-positive ALL sub-group.</p

Impact of age, leukocyte count and day 21-bone marrow response to chemotherapy on the long-term outcome of children with philadelphia chromosome-positive acute lymphoblastic leukemia in the pre-imatinib era: results of the FRALLE 93 study

<p>Abstract</p> <p>Background</p> <p>We explored the heterogeneity of philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL) in a study of the effect of early features on prognosis in children. Here we report the long-term results of the FRALLE 93 study conducted in the era before the use of tyrosine kinase inhibitors.</p> <p>Methods</p> <p>Between 1993 and 1999, 36 children with Ph1-ALL were enrolled into the FRALLE 93 protocol. After conventional four-drug induction, children were stratified by availability of an HLA-matched sibling.</p> <p>Results</p> <p>Complete remission (CR) was observed in 26 children (72%), of which 13 underwent allogeneic bone marrow transplantation (BMT). Thirty-one children were good responders to prednisone, defined on day 8, and 21 were good responders to chemotherapy, defined by day-21 bone marrow (M1). Overall five-year disease-free survival (DFS) was 42 ± 9.7%. Based on multivariate analysis, two groups showed marked differences in five-year outcome: children with age<10, leukocyte count <100,000/mm³and day-21 M1 marrow had a more favorable prognosis (14 pts: 100% CR, event free survival [EFS]: 57%, overall survival [OS]: 79%), than the high-risk group (22 patients: 55% CR, EFS: 18%, OS: 27%) (p < 0.005). We also observed a non statistically significant difference (p = 0.14) in outcome between these groups for transplanted patients (5-year DFS: 83 ± 14% and 33 ± 15%, respectively).</p> <p>Conclusion</p> <p>Age, leukocyte count and early response to treatment defined by the D21 bone marrow response provide an accurate model for outcome prediction. The combination of available tools such as minimal residual disease assessment with determination of these simple factors could be useful for refining indications for BMT in the current era of tyrosine-kinase inhibitor-based therapy.</p

Les dermocorticoides en pédiatrie

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Le déficit en ornithine carbamyl transférase (étude de quatre observations)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Le syndrome de Muckle-Wells, le syndrome CINCA et le familial Cold auto-inflammatory syndrome (un même gène, une même maladie ? Application à travers une famille bretonne)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

DEPISTAGE NEONATAL DE LA DREPANOCYTOSE EN BRETAGNE (BILAN DE LA PREMIERE ANNEE DE FONCTIONNEMENT)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Syndrome de Kasabach-Merritt (prise en charge thérapeutique)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Place des biothérapies dans le traitement des arthrites juvéniles idiopathiques (expérience rennaise)

L'Arthrite Juvénile Idiopathique est l'une des formes fréquentes de rhumatisme chez l'enfant. Une réaction inflammatoire se produit au niveau de la membrance synoviale, sans que l'on connaisse l'antigène responsable. Les biothérapies sont des outils biologiques issus du génie génétique, qui ciblent les molécules responsables de la réaction inflammatoire. Elles neutralisent les cytokines (TNF-a et l'IL-1) ou inhibent les capacités de coopération des lymphocytes T. Dans le traitement des Arthrites Juvéniles Idiopathiques, 6 biothérapies sont utilisées. De nombreuses études démontrent leur efficacité et leur tolérance dans les différentes formes d'arthrites, en s'appuyant sur des critères définis par l'American College of Rheumatology (ACR pédiatrique). Afin d'analyser l'utilisation concrète des biothérapies, j'ai étudié 8 dossiers d'enfants suivis dans le service de pédiatrie du CHU hôpital Sud de Rennes.Juvenile Idiopathic Arthritis is one of the most frequent forms of children's rheumatism. An inflammatory reaction occurs in the synovial membrane, but the responsible antigen is unknown. Biotherapies are biological tools stemming from the genetic engineering, which target inflammatory reaction responsible molecules. They neutralize cytokines or inhibit cooperation capacities of T lymphocytes. In JIA treatment, 6 biotherapies are used. Many studies show their efficiency ans their tolerance in the several arthritis forms, by leaning on criteria defined by the American College of Rheumatology (paediatric ACR) In order to analyse the concrete biotherapies use, I studied 8 children medical files treated in paediatric department of CHU Hôpital Sud.RENNES1-BU Santé (352382103) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Evolution et recours aux soins des enfants atteints de maladie de Crohn et de rectocolite hémorragique en Bretagne (1994-2001)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF