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The t(1;22)(p13;q13) translocation is specifically associated with infant acute megakaryoblastic leukemia (M7). We have recently characterized the two genes involved in this translocation: OTT (One Two Two) and MAL (Megakaryoblastic Acute Leukemia) respectively located on chromosome 1 and 22. The t(1;22) translocation results in the fusion of these genes in all the cases studied to date. We summarize here present knowledge regarding this translocation. [Copyright &y& Elsevier]

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Contexte: La prescription inappropriée d’antibiotiques est un problème majeur à l’hôpital. L’objectif de cette étude était d’évaluer l’impact de mesures éducatives (Guide de prescription des antibiotiques en urgence ou « antibioguide », avis spécialisés par des infectiologues et enseignement semestriel pour les internes) sur la qualité de la prescription des antibiotiques au sein d’un CHU. Méthode: Étude prospective, d’une durée d’un an et demi, ayant inclus 174 patients dans les services de cardiologie, dermatologie et endocrinologie de l’hôpital Nord. Tous les patients inclus ont reçu un traitement antibiotique de mars 2005 à août 2005 (pré intervention) ou de mars 2006 à août 2006 (post intervention) La population a ensuite été séparée en deux groupes : les patients pour lesquels laprescription d’antibiotiques était précisée dans l’antibioguide et les patients pour lesquels la prescription ne l’était pas. La qualité de la prescription a été évaluée par deux seniors impliqués dans le bon usage des antibiotiques. Une prescription d’antibiotiques était considérée comme appropriée lorsque la molécule choisie, la dose, la voie d’administration, l’intervalle d’administration et la durée étaient conformes aux recommandations. Résultats: Après intervention, dans le groupe « protocole », les prescriptions appropriées ont augmenté de 24 % (23 % vs. 47 % ; p = 0,003). En revanche, lorsque les prescriptions n’étaient pas précisées dans l’antibioguide, la qualité de la prescription n’a pas été significativement améliorée. Conclusion: La mise en place d’un guide hospitalier de prescription des antibiotiques renforcé par des avis spécialisés et un enseignement semestriel aux nouveaux internes a permis l’amélioration de la qualité de prescription des antibiotiques pour les indications précisées dans l’antibioguide. [Copyright &y& Elsevier]

CYLD deubiquitinase has been originally defined as a tumor suppressor based exclusively on genetic findings. Indeed, inactivation of CYLD in humans results in familial cylindromatosis and multiple trichoepithelioma, two pathologies characterized by the development of tumors originating specifically from the skin appendages. A set of recent publications has revealed that recurrent inactivation of CYLD occurs through diverse mechanisms in several forms of cancer, unequivocally confirming its tumor suppressor function. This property is associated with the critical role played by CYLD in negatively regulating several signaling pathway, among them the NF-κB signaling pathway., (© 2011 médecine/sciences - Inserm / SRMS.)

The key role of NEMO, the regulatory subunit of IKK, in the NF-kB activation process is firmly established. A series of recent publications suggests that this protein also participates in the genotoxic response, after modification by sumoylation in the nucleus, and coordinates the activation of both NF-kB and IRFs during viral infection, through its interaction with TANK adaptor and TBK1/IKKepsilon kinases.

NF-kappaB is the generic name of a family of transcription factors which play a critical role in the immune, inflammatory and anti-apoptotic responses. Homo- or heterodimers between the five members of the family are retained in the cytoplasm by inhibitory molecules of the IkappaB family, which mask their nuclear localization signal. Three of these inhibitory molecules have been described: IkappaBalpha, IkappaBbeta and IkappaBepsilon. Following cellular stimulation, IkappaB proteins become phosphorylated by the IkappaB kinase (IKK) complex, ubiquitinated and finally degraded by the proteasome. NF-kappaB is then released and translocated to the nucleus, where it activates its target genes by binding to specific sites in their regulatory regions. The IKK complex is constituted of at least three subunits: two kinases, IKKalpha and IKKbeta, and one regulatory subunit (NEMO/IKKgamma), and it constitutes an integrator of most if not all signals which activate NF-kappaB. Although the mechanisms leading to the degradation of the IkappaB proteins are relatively well understood, the precise molecular mechanisms which result in the activation of the high-molecular-weight kinase complex remain to be elucidated. The central role of the IKK complex is consistent with its involvement in a series of human pathologies. We describe here four pathologies: two are due to mutations in the gene encoding the NEMO molecule, a third one in the gene encoding the IkappaBalpha inhibitor, while the fourth one is due to mutations in a gene which had been described as a tumor suppressor. This gene encodes a protein which interacts with NEMO and exhibits deubiquitinase activity, therefore strengthening the recent hypothesis of the role of non-degradation-linked ubiquitination in NF-kappaB activation.

The molecular basis of commitment and differentiation of hematopoietic cells remain poorly understood at the genetic level. Among putative candidates involved in these processes are homeoproteins, a large family of transcription factors which play a major role during development. Using a strategy based on the polymerase chain reaction (PCR) we have isolated nine different Antennapedia-like homeobox (HOX) genes from purified human hematopoietic precursors. Their expression patterns, analyzed with a panel of leukemia-derived cell lines representing various blood cells phenotypes, appears to be lineage-restricted. Extending our study to all the known members of the HOX 1 and HOX 2 clusters, we found that HOX 1 genes are predominantly detected within cell of myelomonocytic origin whereas HOX 2 genes transcripts are principally expressed in erythro-megakaryocytic cell lines. Furthermore, we have observed that the expression of three HOX 1 genes within B lymphoid lineages is stage-related and that the expression of several of them is switched off during TPA-induced differentiation of KG1 and U937 cells. These observations support the idea that homeoproteins could be regulators of lineage determination during hematopoiesis.