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/

Estimation de la séroprévalence du VIH et de l’hépatite C chez les usagers de drogues en France - Premiers résultats de l’enquête ANRS-Coquelicot 2011

International audienceThe second edition of the Coquelicot survey aimed to describre drug users’ (DUs) profiles and practices, estimate HIV and HCV seroprevalences, and assess harm reduction policies. The survey was conducted in 2011 with a method of random sampling including DUs enrolled in specializedservices from five different cities and two departments in France. The eligibility criteria were: having injected or snorted at least once in their life, being at least 18 years old, and speaking French. A blood sample was also collected from to DUs at the end of the interview. Among all DUs selected, 1,568 (75%) accepted to participate. Most of them were men and socially precarious. Mean age was 39 years old. HIV and HCV seroprevalences were respectively 10% and 44%, and varied by age and cities.HCV seroprevalence has decreased since the first edition of the survey in 2004, especially among young DUs (less than 30 years old). HIV seroprevalence remained stable. As injection behaviors are still very strong among the youngest DUs (56% of them under 30 years old had injected at least once in their life, and among them 53% had injected during the month prior to the interview), risk reduction efforts should continue.La deuxième édition de l’enquête Coquelicot avait pour objectifs de décrire les profils et les pratiques des usagers de drogues (UD), d’estimer la séroprévalence du VIH et du VHC, et d’évaluer la politique de réduction des risques.L’enquête s’est déroulée en 2011 à partir d’un échantillon aléatoire d’UD recrutés dans des structures spécialisées de cinq agglomérations et de deux départements français. Les conditions pour pouvoir participer à l’enquête étaient : avoir injecté ou sniffé au moins une fois dans la vie, être majeur et francophone. Un prélèvement biologique a été réalisé auprès des UD ayant répondu au questionnaire. Les premiers résultats montrent un taux de participation de 75%. Avec au final 1 568 personnes enquêtées, l’échantillon se compose en majorité d’hommes. Une grande partie d’entre eux est dans une situation sociale précaire. La moyenne d’âge est de 39 ans. Les séroprévalences du VIH et du VHC sont de 10 et 44 % et varienten fonction de l’âge et de la ville. La séroprévalence du VHC est en baisse depuis la première édition de l’enquête en 2004, en particulier chezles moins de 30 ans. Celle du VIH est stable. Les pratiques d’injection restant importantes chez les plus jeunes (56% des UD de moins de 30 ans ont déjà injecté au cours de la vie, dont 53% dans le dernier mois), les efforts en matière de réduction des risques doivent se poursuivre

No survival improvement in patients with high‐risk multiple myeloma harbouring del(17p) and/or t(4;14) over the two past decades

International audienceNo abstract availabl

Genes Chromosomes Cancer

Myelodysplastic syndromes (MDS) are hematological malignancies classically defined by the presence of cytopenia(s) and dysmorphic myeloid cells. It is now known that MDS can be preceded by a pre-malignant condition called clonal cytopenia of unknown significance (CCUS), which associates a clonality marker with cytopenia in the absence of criteria of dysplasia. However, to date, it is not clear whether chromosomal abnormalities should be considered in the definition of CCUS or if they carry a prognostic impact in CCUS patients. In this study, we analyzed the clinico-biological features and outcomes of 34 patients who presented with one or more cytopenias, an absence of significant dysplasia, and a presence of a chromosomal abnormality (CA). We named this entity chromosomal abnormality with cytopenia of undetermined significance (CACtUS). We show that these patients are slightly older than MDS patients and that they more frequently presented with normocytic anemia. Most CACtUS patients exhibited only one unbalanced CA. The number and type of mutations were comparable between CACtUS patients and MDS patients. Regardless of the cytogenetic abnormality, the clinicobiological characteristics, overall survival, and risk of progression to high-risk (HR) MDS were similar between CACtUS patients and low-risk MDS patients. Thus, we suggest that CACtUS patients can be considered as HR-CCUS and should receive the follow-up regimen recommended for MDS patients

Chromosomal translocations involving the IGH@ locus in B-cell precursor acute lymphoblastic leukemia: 29 new cases and a review of the literature

Chromosomal translocations involving the immunoglobulin heavy chain locus (IGH@) are recurrent but rare in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and various partner genes have been described. Here, we report a new series of 29 cases of BCP-ALL with IGH@ translocations. The partner gene was identified by fluorescence in situ hybridization and/or molecular cloning in 20 patients. Members of the CEBP gene family (n = 11), BCL2 (n = 3), ID4 (n = 3), EPOR (n = 2), and TRA/D@ (n = 1) were identified and demonstrated by quantitative real-time reverse transcriptase-polymerase chain reaction to be markedly up-regulated. The present cases, added to those already reported, confirm the diversity of the partner genes, which, apart from BCL2, are specific to BCP-ALL. Collectively, patients with IGH@ translocations may represent a novel sub-group of BCP-ALL occurring in adolescents and young adults.status: publishe

"Double-hit" chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain

Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (p=0.04), unbalanced translocations (p=0.03) and 8q24 gain (p=0.001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this "double-hit" CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL. This article is protected by copyright. All rights reserved.status: publishe