The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic, and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count, and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A, and CBL genes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1 (also known as Tumor Suppressor in Lung Cancer 1) and NXPE2. CADM1 was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+ cells modifies the lymphoid-to-myeloid ratio in bone marrow, although not altering their multilineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM, and CBL and mutations of ASXL1, SF3B1, and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies

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

Accès au lait de donneuses en Suisse et création de la première banque de lait maternel romande au CHUV ::enjeux et perspectives

Le lait maternel (LM) est idéal pour la croissance et la santé des nourrissons. En l’absence de LM, le lait de donneuses (LD) est préférable au lait artificiel pour les nouveau-nés (NN) à risques, prématurés ou présentant certaines pathologies, au vu de ses effets protecteurs. Les banques de lait (BL) collectent, sécurisent, traitent et distribuent le LD. Il existe en Suisse une insuffisance et une inégalité d’accès au LD, faute de cadre national. Avec le soutien de l’État de Vaud, le CHUV et la Transfusion interrégionale de la Croix-Rouge suisse ouvriront en 2022 la première BL romande. Cette BL propose un système novateur en Suisse, fondé sur une complémentarité d’expertises, afin d’optimiser la qualité et la sécurité du LD et de soutenir la promotion de l’allaitement et du don.Mother’s own milk (MOM) is ideal for infant growth and health. When MOM is unavailable, donor human milk (DHM), rather than infant formula, is recommended for at-risk, preterm or sick neonates (NN), in view of its protective effects. Human milk banks (HMB) collect, secure, process and distribute DHM. In Switzerland, there is insufficient and unequal access to DHM in the absence of a national policy framework. With the support of the State of Vaud, the CHUV and the Interregional Blood Transfusion of the Swiss Red Cross will open the first HMB in Romandy in 2022. This HMB offers an innovative system in Switzerland, based on complementary expertise, in order to guarantee the quality and safety of DHM and to support the promotion of breastfeeding and human milk donation

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

Genetic differences between paediatric and adult Burkitt lymphomas

Dysregulation of MYC is the genetic hallmark of Burkitt lymphoma (BL) but it is encountered in other aggressive mature B-cell lymphomas. MYC dysregulation needs other cooperating events for BL development. We aimed to characterize these events and assess the differences between adult and paediatric BLs that may explain the different outcomes in these two populations. We analysed patterns of genetic aberrations in a series of 24 BLs: 11 adults and 13 children. We looked for genomic imbalances (copy number variations), copy-neutral loss of heterozygosity (CN-LOH) and mutations in TP53, CDKN2A, ID3 (exon 1), TCF3 (exon17) and CCND3 (exon 6). Young patients displayed more frequent 13q31.3q32.1 amplification, 7q32q36 gain and 5q23.3 CN-LOH, while 17p13 and 18q21.3 CN-LOH were only detected in adult BLs. ID3 mutations were present in all adult samples, but only in 42% of childhood cases. CCND3 and ID3 double-hit mutations, as well as 18q21 CN-LOH, seemed to be associated with poorer outcome. For the first time, we report different genetic anomalies between adult and paediatric BLs, suggesting age-related heterogeneity in Burkitt lymphomagenesis. This may explain the poorer prognosis of adult BLs. Additional studies are needed to confirm these results in the setting of clinical trials.status: publishe