1. |
- Langerak, A. W., et al.
(författare)
-
EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations
- 2012
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 26:10, s. 2159-2171
-
Forskningsöversikt (refereegranskat)abstract
- PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
|
|
2. |
- Merabet, S., et al.
(författare)
-
A structurally plastic extension of the homeodomain recognition helix orchestrates central Hox protein activity
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Protein function is encoded within the amino acid coding sequence and the variation in this sequence, and subsequent structure, provide the bases for functional diversification at the molecular and organismal levels. However, how separate protein domainscooperate to build protein activity remains largely unknown. Focusing on three domains of central Hox transcription factors, we mutagenized combinations of their domains to investigate their intrinsic functional organization. Our results demonstrate a high degree of domain interactivity, with an orchestrating role of a structurally plastic C-terminal extension of the homeodomain (HD). This domain provides, in a folding dependant manner, a topologically constrained contact with the Hox cofactor Extradenticle, which impacts the positioning of the recognition helix in the major groove of DNA. These findings provide novel insights in HD/DNA target recognition and, given the phylogeny of this C-terminal extension, also shed light on the molecular bases underlying the functional diversification of paralogous Hox families.
|
|