Deregulation of PAX-5 by translocation of the Emu enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma.

Analyses of the human PAX-5 locus and of the 5' region of the mouse Pax-5 gene revealed that transcription from two distinct promoters results in splicing of two alternative 5' exons to the common coding sequences of exons 2-10. Transcription from the upstream promoter initiates downstream of a TATA box and occurs predominantly in B-lymphocytes, whereas the TATA-less downstream promoter is active in all Pax-5-expressing tissues. The human PAX-5 gene is located on chromosome 9 in region p13, which is involved in t(9;14)(pl3;q32) translocations recurring in small lymphocytic lymphomas of the plasmacytoid subtype and in derived large-cell lymphomas. A previous molecular analysis of a t(9;14) breakpoint from a diffuse large-cell lymphoma (KIS-1) demonstrated that the immunoglobulin heavy-chain (IgH) locus on 14q32 was juxtaposed to chromosome 9p13 sequences of unknown function [Ohno, H., Furukawa, T., Fukuhara, S., Zong, S. Q., Kamesaki, H., Shows, T. B., Le Beau, M. M., McKeithan, T. W., Kawakami, T. & Honjo, T. (1990) Proc. Natl. Acad. Sci. USA 87,628-632]. Here we show that the KIS-1 translocation breakpoint is located 1807 base pairs upstream of exon 1A of PAX-5, thus bringing the potent Emu enhancer of the IgH gene into close proximity of the PAX-5 promoters. These data suggest that deregulation of PAX-5 gene transcription by the t(9;14)(pl3;q32) translocation contributes to the pathogenesis of small lymphocytic lymphomas with plasmacytoid differentiation.

Frequent somatic hypermutation of the 5' noncoding region of the BCL6 gene in B-cell lymphoma.

The BCL6 gene encodes a zinc-finger transcription factor and is altered by chromosomal arrangements in its 5' noncoding region in approximately 30% of diffuse large-cell lymphoma (DLCL). We report here that, in 22/30 (73%) DLCL and 7/15 (47%) follicular lymphoma (FL), but not in other tumor types, the BCL6 gene is also altered by multiple (1.4 x 10(-3) -1.6 x 10(-2) per bp), often biallelic, mutations clustering in its 5' noncoding region. These mutations are of somatic origin and are found in cases displaying either normal or rearranged BLC6 alleles indicating their independence from chromosomal rearrangements and linkage to immunoglobulin genes. These alterations identify a mechanism of genetic instability in malignant B cells and may have been selected during lymphomagenesis for their role in altering BCL6 expression.

The adoption of IPSASs in the Iberian Peninsula: the perspective of the standar-setters

The last decades have been fruitful in reforms in public sector accounting across the world, namely moving from cash-based into accrual-based regimes. In this process of bringing public sector accounting close to business accounting, International Public Sector Accounting Standards (IPSASs) have been developed and adopted in several countries. In the EU context, public sector harmonization among member-States is currently being considered, namely via the development of European Public Sector Accounting Standards (EPSASs). Both IPSASs and EPSASs are understood as, among other things, important to contribute for a more informative and transparent financial reporting of public sector entities and governments. Moreover they are expected to approximate public sector accounting and the National Accounts, hence allowing for more reliable information to monitor fiscal discipline among EU countries. The Iberian countries, after using accrual accounting in the public sector for more than twenty years (Spain from middle 1980s and Portugal from 1990s), have acknowledged the need to embark in an international harmonization process adopting IPSASs, particularly after the adoption of IFRSs in the business sector, which was creating some difficulties for consolidated accounts. Spain has passed the Chart of Accounts for the Public Sector through the Order EHA/1037/2010, which is adapted to IPSASs; Portugal has just passed Law-decree 192/2015, September 11, and is expecting to start implementation in 2017. In both countries a central role in this reform has been assumed by the national standard-setters for public sector accounting. Based on the “Actor Network Theory” to help understanding how and why organizations interact and how this interaction could have an impact on their choice of accounting policies, this paper aims to analyse, from the Iberian public sector accounting standard-setters perspective, how the adoption/adaptation of IPSASs has been considered and developed in these countries. Research questions to be considered are the following, which will be asked in interviews to the members of the standard-setting committees in both Portugal and Spain: • What were the driving forces leading to the decision to adopt and implement IPSASs? • Which other governmental bodies’ experiences, if any, were considered in the adoption of IPSASs? • What specific steps were/are being undertaken to prepare for the conversion from the existing system to IPSASs? • What were/are the institutional challenges faced/expected to face? • What assistance have been received from IFAC and/or IPSASB, or from other sources, if any, throughout the adoption/implementation? • How can the success of the adoption/implementation be characterised? • What benefits can/have the government derive/derived from the adoption and implementation of IPSASs? The paper is expected to contribute to the understanding of the issues underlying the process of embarking in public sector accounting reforms towards IPSASs.