Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis

A Rare Extraskeletal Osteosarcoma Appearing After 55 Years on a Large Stage 3 Burn Scar

It is widely accepted that chronic burn wounds may lead to the development of various malignant skin tumors. Deep stage 3 burned areas may facilitate deeper carcinogenesis. Deep tissues are probably less subject to severe insult than is the epithelial layer during physical insult, suggesting that soft tissues transform to a lesser extent during the late stages of tumoral development as in an immunocompromised district with altered local immune defense with both cellular and humoral defense affected. Most authors claim that tumors are almost squamous cell carcinomas, although other types of malignancies such as basal cell carcinoma and, to a lesser extent, melanoma can also be seen. However, malignant transformation of cutaneous soft tissue in a burn insult area has rarely been described. Similarly, burn-induced tumors of histiocytic origin have been reported in few cases and osteosarcoma only in two case reports. Here, we report a patient case suffering from severe large stage 3 burn after-effects on the leg. Fifty-five years after the injury, this patient developed a large extraosseous osteosarcoma on the scar

Halo Nevi Are Not Trivial: About 2 Young Patients of Regressed Primary Melanoma That Simulates Halo Nevi.

Halo nevi are often considered benign, and the possibility of malignancy is not always clear to practitioners. We present two case reports suggesting that a halo nevus appearance can be seen in melanoma, even in young adults. A literature search for halo nevi revealing melanoma shows that this is a very rare condition. . This report of two young patients indicates the importance of obtaining a detailed history to detect warning signs such as itching, pain, spontaneous bleeding, and previous alterations according to the patient, including a previously totally black colour in an already fully regressed melanoma. The risk of a halo nevus being malignant is higher if there is only one unique halo nevus and no personal or familial history of vitiligo. We postulate that a regressing atypical nevus or a regressing melanoma may be induced by an immunologic reaction as halo nevus type of clinical picture

Anti-IL-17A Autovaccination Prevents Clinical and Histological Manifestations of Experimental Autoimmune Encephalomyelitis

Excessive or inappropriate production of IL-17A has been reported in diseases such as rheumatoid arthritis, asthma, and multiple sclerosis. The potential clinical relevance of these correlations was suggested by the protective effects of anti-IL-17A monoclonal antibodies in various mouse disease models. However, the chronic nature of the corresponding human afflictions raises great challenges for Ab-based therapies. An alternative to passive Ab therapy is autovaccination. Covalent association of self-cytokines with foreign proteins has been reported to induce the production of antibodies capable of neutralizing the biological activity of the target cytokine. We recently reported that cross-linking of IL-17A to ovalbumin produced highly immunogenic complexes that induced long-lasting IL-17A-neutralizing antibodies. Vaccinated SJL mice were completely protected against experimental autoimmune encephalomyelitis (EAE) induced by proteolipid protein peptide (PLP 139-151), and a monoclonal anti-IL-17A Ab (MM17F3), derived from C57Bl/6 mice vaccinated against IL-17A-OVA, also prevented disease development. Here we report that this Ab also protects C57Bl/6 mice from myelin oligdendrocyte glycoprotein (MOG)-induced EAE. Histological analysis of brain sections of C57Bl/6 mice treated with MM17F3 showed a complete absence of inflammatory infiltrates and evidence for a marked inhibition of chemokine and cytokine messages in the spinal cord. These results further extend the analytical and therapeutic potential of the autovaccine procedure

Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium.

Rituximab displays therapeutic benefits in the treatment of patients with rheumatoid arthritis (RA) resistant to tumor necrosis factor (TNF) blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. We undertook this study to investigate the global molecular effects of rituximab in synovial biopsy samples obtained from anti-TNF-resistant RA patients before and after administration of the drug

Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules

Most antigenic peptides presented by MHC class I molecules result from the degradation of intracellular proteins by the proteasome. In lymphoid tissues and cells exposed to IFNγ, the standard proteasome is replaced by the immunoproteasome, in which all of the standard catalytic subunits β1, β2, and β5 are replaced by their inducible counterparts β1i, β2i, and β5i, which have different cleavage specificities. The immunoproteasome thereby shapes the repertoire of antigenic peptides. The existence of additional forms of proteasomes bearing a mixed assortment of standard and inducible catalytic subunits has been suggested. Using a new set of unique subunit-specific antibodies, we have now isolated, quantified, and characterized human proteasomes that are intermediate between the standard proteasome and the immunoproteasome. They contain only one (β5i) or two (β1i and β5i) of the three inducible catalytic subunits of the immunoproteasome. These intermediate proteasomes represent between one-third and one-half of the proteasome content of human liver, colon, small intestine, and kidney. They are also present in human tumor cells and dendritic cells. We identified two tumor antigens of clinical interest that are processed exclusively either by intermediate proteasomes β5i (MAGE-A3271–279) or by intermediate proteasomes β1i-β5i (MAGE-A10254–262). The existence of these intermediate proteasomes broadens the repertoire of antigens presented to CD8 T cells and implies that the antigens presented by a given cell depend on their proteasome content