A Waldenström-macroglobulinaemia és betegségre szabott kezelése | Waldenström’s macroglobulinemia and its individualized therapy options

Absztrakt: A Waldenström-féle macroglobulinaemia egy jellemzően a csontvelőben terjedő lymphoplasmocytás lymphoma és következményes monoklonális IgM-hiperszekréció okozta klinikai tünetegyüttes. A közelmúlt eredményei rámutattak, hogy a betegség legalább három eltérő patobiológiájú és klinikai viselkedésű formájában jelentkezhet. A MYD88 95–97%-os gyakoriságú mutációi mellett 30–40%-os gyakorisággal megjelenhetnek CXCR4-mutációk, 17%-ban ARID1A-mutációk és 10% körüli gyakorisággal CD79B-mutációk. A CXCR-jelátvitel képes a MYD88-aktiváció fokozta tumorszuppresszorgén-működés elnémítására. A MYD88- és CXCR4-mutációk együttes előfordulása nagyobb tumortömeget, kezeléskor lassabban kialakuló és kevésbé mély választ eredményez, gyakoribb rezisztenciával. Összefoglalónkban a legújabb adatok birtokában kívánunk támpontot nyújtani a szimptomatikus betegség kezelésekor megkívánt kezelési protokoll megválasztásához. Orv Hetil. 2017; 158(41): 1604–1614. | Abstract: Waldenström’s macroglobulinaemia is a form of lymphoplasmocytic lymphoma that preferentially localizes to the bone marrow and causes a special syndrome characterized by monoclonal IgM hypersecretion. Recent results point to the fact that this disease has at least three different pathobiological forms with different clinical presentation. While mutations of MYD88 occur in 95–97% of the cases, there are CXCR4 mutations in 30–40%, ARID1A mutations in 17% and CD79B mutations in approximately 10% of afflicted individuals. CXCR pathway signaling is able to transcriptionally silence tumor suppressors induced by MYD88 activation. Patients with mutated MYD88 and CXCR4 present with higher tumor burden, slower developing and less deep response upon therapy with more frequent resistance. In this review, based on the most recent data, a treatment selection advice is provided for the therapy of symptomatic patients. Orv Hetil. 2017; 158(41): 1604–1614

Correlation between DNA ploidy, metaphase high-resolution comparative genomic hybridization results and clinical outcome of synovial sarcoma

<p>Abstract</p> <p>Background</p> <p>Although synovial sarcoma is the 3rd most commonly occurring mesenchymal tumor in young adults, usually with a highly aggressive clinical course; remarkable differences can be seen regarding the clinical outcome. According to comparative genomic hybridization (CGH) data published in the literature, the simple and complex karyotypes show a correlation between the prognosis and clinical outcome. In addition, the connection between DNA ploidy and clinical course is controversial. The aim of this study was using a fine-tuning interpretation of our DNA ploidy results and to compare these with metaphase high-resolution CGH (HR-CGH) results.</p> <p>Methods</p> <p>DNA ploidy was determined on Feulgen-stained smears in 56 synovial sarcoma cases by image cytometry; follow up was available in 46 cases (average: 78 months). In 9 cases HR-CGH analysis was also available.</p> <p>Results</p> <p>10 cases were found DNA-aneuploid, 46 were DNA-diploid by image cytometry. With fine-tuning of the diploid cases according to the 5c exceeding events (single cell aneuploidy), 33 cases were so called "simple-diploid" (without 5c exceeding events) and 13 cases were "complex-diploid"; containing 5c exceeding events (any number). Aneuploid tumors contained large numbers of genetic alterations with the sum gain of at least 2 chromosomes (A-, B- or C-group) detected by HR-CGH. In the "simple-diploid" cases no or few genetic alterations could be detected, whereas the "complex-diploid" samples numerous aberrations (equal or more than 3) could be found.</p> <p>Conclusions</p> <p>Our results show a correlation between the DNA-ploidy, a fine-tuned DNA-ploidy and the HR-CGH results. Furthermore, we found significant correlation between the different ploidy groups and the clinical outcome (p < 0.05).</p