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Chromosomal aberrations of T-cell receptor (TCR) gene loci often involve the TCRαδ (14q11) locus and affect various known T-cell oncogenes. A systematic fluorescent in situ hybridization (FISH) screening for the detection of chromosomal aberrations involving the TCR loci, TCRαδ (14q11), TCRβ (7q34) and TCRγ (7p14), has not been conducted so far. Therefore, we initiated a screening of 126 T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma cases and 19 T-ALL cell lines using FISH break-apart assays for the different TCR loci. Genomic rearrangements of the TCRβ locus were detected in 24/126 cases (19%), most of which (58.3%) were not detected upon banding analysis. Breakpoints in the TCRαδ locus were detected in 22/126 cases (17.4%), whereas standard cytogenetics only detected 14 of these 22 cases. Cryptic TCRαδ/TCRβ chromosome aberrations were thus observed in 22 of 126 cases (17.4%). Some of these chromosome aberrations target new putative T-cell oncogenes at chromosome 11q24, 20p12 and 6q22. Five patients and one cell line carried chromosomal rearrangements affecting both TCRβ and TCRαδ loci. In conclusion, this study presents the first inventory of chromosomal rearrangements of TCR loci in T-ALL, revealing an unexpected high number of cryptic chromosomal rearrangements of the TCRβ locus and further broadening the spectrum of genes putatively implicated in T-cell oncogenesis.

Ehlers–Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from mutations inactivating ADAMTS-2, an enzyme excising the aminopropeptide of procollagens type I, II, and III. All previously described mutations create premature stop codons leading to a marked reduction in the level of mRNA. In this study, we analyzed the ADAMTS2 cDNA sequences from five patients displaying clinical and/or biochemical features consistent with a diagnosis of either typical or potentially mild form of EDS type VIIC. Three different alterations were detected in the two patients with typical EDS type VIIC. The first patient was homozygous for a genomic deletion causing an in-frame skipping of exons 3–5 in the transcript. In the second patient, the allele inherited from the mother lacks exon 3, generating a premature stop codon, whereas the paternal allele has a genomic deletion resulting in an in-frame skipping of exons 14–16 at the mRNA level. Although the exons 3–5 or 14–16 encode protein domains that have not been previously recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired in vitro and in vivo, providing evidence for the requirement of these domains for proper enzyme function. The three other patients with a phenotype with some resemblance to EDS type VIIC only had silent and functionally neutral variations also frequently found in a normal population.

Thirty cases of acute myeloid leukaemia (AML) with MYST histone acetyltransferase 3 (MYST3) rearrangement were collected in a retrospective study from 14 centres in France and Belgium. The mean age at diagnosis was 59.4 years and 67% of the patients were females. Most cases (77%) were secondary to solid cancer (57%), haematological malignancy (35%) or both (8%), and appeared 25 months after the primary disease. Clinically, cutaneous localization and disseminated intravascular coagulation were present in 30 and 40% of the cases, respectively. AMLs were myelomonocytic (7%) or monocytic (93%), with erythrophagocytosis (75%) and cytoplasmic vacuoles (75%). Immunophenotype showed no particularity compared with monocytic leukaemia without MYST3 abnormality. Twenty-eight cases carried t(8;16)(p11;p13) with MYST3-CREBBP fusion, one case carried a variant t(8;22)(p11;q13) and one case carried a t(8;19)(p11;q13). Type I ( MYST3 exon 16- CREBBP exon 3) was the most frequent MYST3-CREBBP fusion transcript (65%). MYST3 rearrangement was associated with a poor prognosis, as 50% of patients deceased during the first 10 months. All those particular clinical, cytologic, cytogenetic, molecular and prognostic characteristics of AML with MYST3 rearrangement may have allowed an individualization into the World Health Organization classification.

Willingness to pay (WTP) is used to assess individuals’ value attribution to health-related quality of life interventions. Little is known about predictors of WTP for sport and physical activity in socially vulnerable groups in community-based physical activity (CBHEPA) programs. This study addresses the questions: What is the WTP for sport and physical activity of participants in CBHEPA programs, expressed in WTP money and WTP time ? Which factors predict WTP money and WTP time ? From the literature, predictors for WTP for sport and physical activity were identified: (1) personal and socio-economic predictors: income, education, age, and ethnic origin, (2) health-related predictors: perceived health, life satisfaction, sense of coherence, self-efficacy, (3) sport and physical activity-related predictors: duration and frequency of participation, leisure-time sport or physical activity, sport club membership, enjoyment, and membership fee. Data were gathered for WTP money and WTP time (n = 268) in 19 groups in an evaluation study of CBHEPA programs. Ordered probit was used for analyses. WTP money was a monthly average of €9.6. WTP time was on average 17.6 min travel time. Income was found as predictor for both WTP money and WTP time . Other predictors for WTP money were: duration and frequency of program participation, enjoyment, and (former) sport club membership. Low income and younger age were found as predictors for WTP time . Predictors for WTP money are related to income and sport and physical activity experiences, for WTP time to income and age. Short-term program satisfaction is probably more decisive for WTP money than long-term perspectives of improving health-related quality of life.

A series of 38 patients with acute myeloblastic leukemia (AML) with 49 or more chromosomes and without structural abnormalities was selected within the Groupe Francophone de Cytogénétique Hématologique (GFCH) to better define their characteristics. The median age of the patients was 65 years, and all FAB subtypes were represented. Although all chromosomes were gained, some seems to prevail: chromosome 8 (68%), 21 (47%), 19 (37%), and 13 and 14 (34% each). Since MLL rearrangement leads patients in a group with an unfavorable prognosis, search for cryptic rearrangements of MLL was performed in 34 patients and showed abnormalities in 5 (15%). When we applied the most frequent definition of complex karyotypes (three or more abnormalities), all patients with high hyperdiploid AML fall in the unfavorable category. Among the 18 patients without MLL rearrangement receiving an induction therapy, 16 (89%) reached CR and 6 (33%) were still alive after a 31-month median follow-up (14–61 months). Although this study was retrospective, these results suggest that high hyperdiploid AML without chromosome rearrangement seems to be a subgroup of uncommon AML (less than 1%), and may be better classified in the intermediate prognostic group.

Using a two-step procedure involving insertional gene targeting and recombinase-mediated cassette exchange in ES cells, we have produced two lines of transgenic mice expressing a dominant-negative latency-associated myostatin propeptide under control of the myosin light chain 1F promoter and 1/3 enhancer from the TSPY locus on the Y chromosome. Males of the corresponding lines are characterized by a 5-20% increase in skeletal muscle mass. This experiment demonstrates the feasibility of a more efficient cattle production system combining superior beef production abilities for bulls and dairy abilities for cows.

To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Français de Cytogénétique Hématologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included (211 children ⩽15 years and 153 adults), and 67 (18.5%) [47 children (22.4%) and 20 adults (13.1%)] were shown to either harbor the t(5;14)q35;q32) translocation or express the HOX11L2 gene or both. Most of the common hematological parameters did not show significant differences within positive and negative populations, whereas the incidence of CD1a+/CD10+ and cytoplasmic CD3+ patients was significantly higher in positive than in negative children. Out of the 63 positive patients investigated by conventional cytogenetics, 32 exhibited normal karyotype, whereas the others 31 showed clonal chromosome abnormalities, which did not include classical T-ALL specific translocations. Involvement of the RANBP17/HOX11L2 locus was ascertained by fluorescence in situ hybridization in six variant or alternative (three-way translocation or cytogenetic partner other than 14q32) translocations out of the 223 patients. Our results also show that HOX11L2 expression essentially occurs as a result of a 5q35 rearrangement, but is not associated with another identified T-ALL specific recurrent genetic abnormality, such as SIL-TAL fusion or HOX11 expression.