Defining signatures of peripheral T-cell lymphoma with a targeted 20-marker gene expression profiling assay.

Peripheral T-cell lymphoma comprises a heterogeneous group of mature non-Hodgkin lymphomas. Their diagnosis is challenging, with up to 30% of cases remaining unclassifiable and referred to as "not otherwise specified". We developed a reverse transcriptase-multiplex ligation-dependent probe amplification gene expression profiling assay to differentiate the main T-cell lymphoma entities and to study the heterogeneity of the "not specified" category. The test evaluates the expression of 20 genes, including 17 markers relevant to T-cell immunology and lymphoma biopathology, one Epstein-Barr virus-related transcript, and variants of RHOA (G17V) and IDH2 (R172K/T). By unsupervised hierarchical clustering, our assay accurately identified 21 of 21 ALK-positive anaplastic large cell lymphomas, 16 of 16 extranodal natural killer (NK)/T-cell lymphomas, 6 of 6 hepatosplenic T-cell lymphomas, and 13 of 13 adult T-cell leukemia/lymphomas. ALK-negative anaplastic lymphomas (n=34) segregated into one cytotoxic cluster (n=10) and one non-cytotoxic cluster expressing Th2 markers (n=24) and enriched in DUSP22-rearranged cases. The 63 T <sub>FH</sub> -derived lymphomas divided into two subgroups according to a predominant T <sub>FH</sub> (n=50) or an enrichment in Th2 (n=13) signatures. We next developed a support vector machine predictor which attributed a molecular class to 27 of 77 not specified T-cell lymphomas: 17 T <sub>FH</sub> , five cytotoxic ALK-negative anaplastic and five NK/T-cell lymphomas. Among the remaining cases, we identified two cell-of-origin subgroups corresponding to cytotoxic/Th1 (n=19) and Th2 (n=24) signatures. A reproducibility test on 40 cases yielded a 90% concordance between three independent laboratories. This study demonstrates the applicability of a simple gene expression assay for the classification of peripheral T-cell lymphomas. Its applicability to routinely-fixed samples makes it an attractive adjunct in diagnostic practice

Mapping thermal emission in the synchrotron-dominated SNRs 330.2+1.0, 3C58, and RX J1713.7-3946

International audienceSince the discovery of synchrotron X-ray emission from the shell of the supernova remnant (SNR) SN 1006, multiple observations from Chandra and XMM-Newton have shown that many young SNRs produce synchrotron emission in X-rays. Among those, a few peculiar SNRs have their X-ray emission largely dominated by synchrotron radiation, showing no or only faint traces of thermal emission. In this paper, we report our mapping of the thermal emission in three emblematic synchrotron-dominated SNRs: G330.2+1.0, 3C58, and RX J1713.7-3946. We used a blind source separation method able to retrieve faint components from X-ray data in the form of Chandra and XMM-Newton observations. The thermal candidates disentangled by the algorithm were then used to select regions of extraction. We then analyzed the extracted spectra to assess their physical nature. We conclude that the components retrieved by the algorithm indeed represent the spatial distribution of the thermal emission in G330.2+1.0 and 3C58, and a likely thermal candidate in RX J1713.7-3946. Our findings confirm and expand on past studies

The X-ray synchrotron rims in Cassiopeia A narrow with energy

Context. Some young supernova remnants exhibit thin filaments of X-ray synchrotron radiation coinciding with the forward shock due to accelerated electrons interacting with the local magnetic field. The two main models accounting for the radial brightness evolution of these filaments differ in their prediction of the narrowing (or not) of the filaments with increasing photon energy. Aims. In this paper, we report our observation of such a narrowing of the synchrotron filaments in Cassiopeia A at X-ray energies, and how this finding could inform our understanding of the mechanisms at stake in their formation. Methods. We used a new blind-source-separation method on the 1 Ms Chandra observation of Cassiopeia A in order to obtain detailed and unpolluted images of the synchrotron emission in three energy bands. We then extracted the profiles of several filaments at the forward shock and the reverse shock to estimate and compare their widths. Results. We find that there is indeed a narrowing with energy of the synchrotron filaments both at the forward and at the reverse shocks in Cassiopeia A. The energy dependency of this narrowing seems stronger at high energy, which is indicative of a damping effect that is also suggested by radio observations

The X-ray synchrotron rims in Cassiopeia A narrow with energy

International audienceSome young supernova remnants exhibit thin filaments of X-ray synchrotron radiation coinciding with the forward shock due to accelerated electrons interacting with the local magnetic field. The two main models accounting for the radial brightness evolution of these filaments differ in their prediction of the narrowing (or not) of the filaments with increasing photon energy. In this paper, we report our observation of such a narrowing of the synchrotron filaments in Cassiopeia A at X-ray energies, and how this finding could help in understanding the mechanisms at stake in their formation. We used a new blind source separation method on the 1 Ms Chandra observation of Cassiopeia A, in order to obtain detailed and unpolluted images of the synchrotron emission in three energy bands. We then extracted the profiles of several filaments at the forward shock and the reverse shock to estimate and compare their widths. We find that there is indeed a narrowing with energy of the synchrotron filaments both at the forward and at the reverse shocks in Cassiopeia A. The energy dependency of this narrowing seems stronger at high energy, which is indicative of a damping effect, confirmed by radio observations

Rapid Expansion of the Young Type Ia Supernova Remnant 0519–69.0: More Evidence for a Circumstellar Shell

The nature of Type Ia supernovae remains controversial. The youngest remnants of Ia supernovae hold clues to the explosion and to the immediate surroundings. We present a third epoch of Chandra observations of the ∼600 yr old Type Ia remnant 0519–69.0 in the Large Magellanic Cloud, extending the time baseline to 21 yr from the initial 2000 observations. We find rapid expansion of X-ray emitting material, with an average velocity of 4760 km s ^−1 . At the distance of the LMC, this corresponds to an undecelerated age of 750 yr, with the true age somewhat lower. We also find that the bright ring of emission has expanded by 1.3%, corresponding to a velocity of 1900 km s ^−1 and an undecelerated age of 1600 yr. The high velocity of the peripheral X-rays, contrasted with the modest expansion of the main X-ray shell, provides further evidence for a massive shell of circumstellar material

Chromosomal rearrangements involving the BCL3 locus are recurrent in classical Hodgkin and peripheral T-cell lymphoma

In a recent issue of Blood, Mathas et al suggested elevated BCL3 expression to be functionally important in classical Hodgkin lymphoma (cHL) and peripheral T-cell lymphoma (PTCL). The authors reported strong BCL3 protein expression in the vast majority of cHLs and a subset of PTCLs.1 These results corroborated similar immunohistochemical findings by Canoz et al. Mathas et al reported chromosomal gains of the BCL3 locus in chromosome band 19q13 as a potential cause of BCL3 upregulation in 3 of 6 cHL cell lines and 8 of 37 PTCLs. Here, we provide evidence that not only chromosomal gains but also translocations affecting the BCL3 locus are recurrent in cHL and PTCL. [beginning of text