{"id":25890,"date":"2022-10-23T18:54:23","date_gmt":"2022-10-23T16:54:23","guid":{"rendered":"https:\/\/www.mylav.net\/nekategorizirano-sl\/mutational-analysis-of-tp53-a-new-frontier-in-the-clinical-management-of-diffuse-large-b-cell-lymphoma-dlbcl-in-dogs\/"},"modified":"2024-02-09T10:57:02","modified_gmt":"2024-02-09T09:57:02","slug":"mutacijska-analiza-gena-tp53-nova-granica-u-klinickom-lijecenju-difuznog-limfoma-velikih-b-limfocita-dlbcl-u-pasa","status":"publish","type":"post","link":"https:\/\/www.mylav.net\/hr\/blog-hr\/mutacijska-analiza-gena-tp53-nova-granica-u-klinickom-lijecenju-difuznog-limfoma-velikih-b-limfocita-dlbcl-u-pasa\/","title":{"rendered":"MUTACIJSKA ANALIZA GENA TP53: NOVA GRANICA U KLINI\u010cKOM LIJE\u010cENJU DIFUZNOG LIMFOMA VELIKIH B-LIMFOCITA (DLBCL) U PASA"},"content":{"rendered":"

Napokon smo stigli<\/strong>: mo\u017eemo po\u010deti s rutinskom procjenom mutacijskog stanja novotvorina kod psa. U ovom \u0107emo \u010dlanku pogledati \u0161to se mo\u017ee u\u010diniti i kako mo\u017eemo upotrijebiti mutacijsku analizu gena TP53 kod pasa s DLBCL-om.<\/p>\n

DLBCL \u2013 naj\u010de\u0161\u0107i limfom u pasa<\/h4>\n

Od limfoproliferativnih bolesti pasa DLBCL je naj\u010de\u0161\u0107i izotip i predstavlja oko 70 % svih limfoma u toj \u017eivotinjskoj vrsti.<\/p>\n

DLBCL pokazuje prili\u010dno agresivno biolo\u0161ko pona\u0161anje i uglavnom se pojavljuje kao multicentri\u010dni \u010dvor te zahva\u0107a vi\u0161e sekundarnih limfnih organa. U naprednijim klini\u010dkim stadijima bolesti opa\u017ea se i infiltracija ciljnih organa, uklju\u010duju\u0107i jetru, slezenu, ko\u0161tanu sr\u017e i perifernu krv.<\/p>\n

Prema kriterijima klasifikacije limfoma pasa koje je pripremila Svjetska zdravstvena organizacija (WHO) nodalni DLBCL karakterizira nekontroliran i \u0161iroko ra\u0161iren rast populacije neoplasti\u010dnih stanica u limfnim \u010dvorovima, pri \u010demu je normalna anatomija organa potpuno naru\u0161ena.<\/p>\n

Neoplasti\u010dne su stanice srednje\/velike veli\u010dine i vrlo \u010desto imaju vi\u0161e perifernih jezgrica ili jednu sredi\u0161nju jezgricu. Ta se populacija mo\u017ee pripisati centroblastima i imunoblastima (SL. 1). Neoplasti\u010dni su limfociti B-stanice imunofenotipa i identificiraju se putem imunohistokemijskog testa koji pokazuje pozitivne rezultate za CD20, CD79 ili PAX5 (SL. 1). Na kraju, prva linija lije\u010denja predvi\u0111a CHOP kemoterapiju (ciklofosfamid, hidroksidaunorubicin, onkovin, prednizon) uz mogu\u0107i dodatak APAVAC-a u re\u017eimu kemo\/imunoterapije.<\/p>\n

\"Histolo\u0161ki
Slika 1 – Klasi\u010dni mikroskopski\/citolo\u0161ki prikaz DLBCL-a u pasa. Prevladava populacija srednjeg\/velikog limfoidnog tkiva s jasno vidljivim jezgricama i vrlo bazofilnom citoplazmom<\/figcaption><\/figure>\n
\"Histolo\u0161ki
Slika 2 – Histolo\u0161ki i imunohistokemijski test DLBCL-a u pasa. \u010cini se da limfni \u010dvor ima ve\u0107i broj infiltracija neoplasti\u010dne populacije, \u0161to mijenja normalnu arhitekturu organa (slika lijevo). Neoplasti\u010dne stanice su pozitivne na CD20 (marker B-limfocita) u imunohistokemijskom testu (slika desno)<\/figcaption><\/figure>\n

DLBCL \u2013 klini\u010dka\/patolo\u0161ka klasifikacija<\/h4>\n

Povijesno gledano, DLBCL je bio uvr\u0161ten me\u0111u limfome \u201evisokog stupnja\u201d ili \u201eagresivne\u201d limfome, ali zadnjih su godina tijekom istra\u017eivanja u veterinarskoj onkologiji prona\u0111eni novi ciljevi i terapijski pristupi, koji su omogu\u0107ili pobolj\u0161anje stopa pre\u017eivljenja i intervala bez bolesti u pasa oboljelih tim tumorom.<\/p>\n

Me\u0111utim, na\u017ealost, odgovor<\/strong> na lije\u010denje i dalje je vrlo varijabilan<\/strong> i te\u0161ko ga je predvidjeti pri postavljanju dijagnoze. Neki psi ostaju u klini\u010dkoj remisiji samo nekoliko mjeseci nakon lije\u010denja, drugi imaju mnogo dulja razdoblja remisije i pre\u017eivljenja; u nekim slu\u010dajevima nekoliko godina.<\/p>\n

Takvo raznoliko biolo\u0161ko pona\u0161anje djelomi\u010dno se obja\u0161njava odre\u0111enim mjerljivim klini\u010dkim varijablama<\/strong>, kao \u0161to su stadij, klini\u010dki podstadij i neoplasti\u010dna infiltracija ko\u0161tane sr\u017ei putem testiranja proto\u010dnom citofluorimetrijom. Iako su vrlo korisni, ti parametri ne omogu\u0107uju uvijek uvid u prognozu \u017eivotinje. Zapravo, druge varijable mogle bi biti va\u017ene, kao \u0161to je uloga imunolo\u0161kog sustava u odgovoru na lije\u010denje i genetski ili molekularni profil samog tumora.<\/p>\n

DLBCL \u2013 genetska klasifikacija, na dobrom smo putu!<\/h4>\n

Stoga je jasno da sama klini\u010dka\/patolo\u0161ka klasifikacija vi\u0161e nije dovoljna za klini\u010dku karakterizaciju DLBCL-a u pasa. Upravo iz tog razloga, paralelno s humanom medicinom, ispitivanja DLBCL-a kod pasa zadnjih su godina uglavnom bila usredoto\u010dena na obja\u0161njavanje molekularnih i genetskih mehanizama koji su u osnovi razvoja i napredovanja bolesti.<\/p>\n

Identificirane su razli\u010dite aberacije u genima<\/strong> koji sudjeluju u mehanizmima stani\u010dne aktivacije, diferencijacije i proliferacije. U nekim slu\u010dajevima otkrivene su mutacije<\/strong> u DNK-u, \u0161to potencijalno zna\u010di da su limfoidne stanice sposobne za br\u017eu proliferaciju, izbje\u0107i imunolo\u0161ku kontrolu i oduprijeti se programiranoj stani\u010dnoj smrti (apoptozi). U nekim su slu\u010dajevima te mutacije bile povezane s klini\u010dkim varijablama i odgovorom na lije\u010denje.<\/p>\n

U jednom ispitivanju iz 2022. (Giannuzzi et al., 2022.) otkriveno je da su mutacije gena TP53<\/strong> negativan i neovisan prognosti\u010dki<\/strong> \u010dimbenik u DLBCL-u kod pasa.<\/p>\n

Zbog svoje uloge, TP53 je nedavno definiran kao \u201e\u010duvar genoma\u201d, naziv upu\u0107uje na njegovu sposobnost popravljanja o\u0161te\u0107enog DNK-a zaustavljanjem rasta stanica, induciranjem apoptoze i stani\u010dnog starenja. Stoga je lako shvatiti kako bi u neoplasti\u010dnom ili predneoplasti\u010dnom kontekstu eventualne mutacije tog gena mogle potisnuti aktivnost i potaknuti karcinogenezu.<\/p>\n

DLBCL \u2013 analiza gena TP53 kod pasa s DLBCL-om: \u0161to u\u010diniti!<\/h4>\n

Kod pasa sa suspektnim oblikom DLBCL-a, na temelju citolo\u0161kog i citometrijskog testa pove\u0107anog limfnog \u010dvora uvijek \u0107e biti potrebno napraviti histolo\u0161ki i imunohistokemijski test (CD3, CD20) cijelog uklonjenog limfnog \u010dvora radi definitivne potvrde.<\/p>\n

Kad se provodi limfadenektomija, bit \u0107e va\u017eno izolirati mali fragment<\/strong> neoplasti\u010dnog tkiva (0,5 cm3 \u2013 veli\u010dine bombona \u201etic tac\u201d) i pohraniti ga u epruvetu s fiziolo\u0161kom otopinom za analizu mutacije<\/strong> gena TP53 (sl.2)
\nEpruvetu treba poslati u laboratorij u roku od 24 do 48 sati na testiranje. U isto vrijeme, uvijek je potrebno poslati uzorak krvi u EDTA epruveti (sl.3)<\/p>\n

\"Za
Slika 3 – Za analizu mutacije, u MYLAV mora biti poslana biopsija linfnog \u010dvora u fiziolo\u0161koj otopini i uzorak periferne krvi pacijenata sa DLBCL-om potvrdjenog histolo\u0161ki i imunohistokemijski<\/figcaption><\/figure>\n

Dakle, na temelju rezultata klini\u010dkog odre\u0111ivanja stadija, histopatolo\u0161kog\/imunohistokemijskog testiranja i probira gena TP53, bit \u0107e mogu\u0107e konzultirati prognosti\u010dki algoritam izra\u0111en pomo\u0107u istra\u017eivanja Giannuzzija et al. (posjetite svoje rezervirano podru\u010dje na web stranici MYLAV-a.)<\/p>\n

Ovaj se algoritam mo\u017ee upotrebljavati i za odre\u0111ivanje najboljeg tretmana na temelju odabranih klini\u010dkih varijanti. <\/p>\n

\n
Bibliografija<\/h5>\n

Diana Giannuzzi\u200a, Laura Marconato, Antonella Fanelli\u200a, Luca Licenziato, Raffaella De Maria, Andrea Rinaldi, Luca Rotta\u200a, Nicole Rouquet, Giovanni Birolo, Piero Fariselli, Afua A. Mensah, Francesco Bertoni\u200a and Luca Aresu. (2022) The genomic landscape of canine diffuse large B-cell lymphoma identifies distinct subtypes with clinical and therapeutic implications. Lab Animals 51: 191 \u2013 202.<\/p>\n

Luca Aresu<\/strong>, Sveu\u010dili\u0161te u Torinu, voditelj tima patologije u MYLAV-u
\nWalter Bertazzolo<\/strong>, Med. vet. Europski specijalist veterinarske klini\u010dke patologije (EBVS) (dipl. ECVCP); znanstveni direktor MYLAV-a\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Napokon smo stigli: mo\u017eemo po\u010deti s rutinskom procjenom mutacijskog stanja novotvorina kod psa. U ovom […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[805],"tags":[],"class_list":["post-25890","post","type-post","status-publish","format-standard","hentry","category-blog-hr"],"acf":[],"yoast_head":"\nMUTACIJSKA ANALIZA GENA TP53: NOVA GRANICA U KLINI\u010cKOM LIJE\u010cENJU DIFUZNOG LIMFOMA VELIKIH B-LIMFOCITA (DLBCL) U PASA - MyLav<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.mylav.net\/hr\/blog-hr\/mutacijska-analiza-gena-tp53-nova-granica-u-klinickom-lijecenju-difuznog-limfoma-velikih-b-limfocita-dlbcl-u-pasa\/\" \/>\n<meta property=\"og:locale\" content=\"hr_HR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"MUTACIJSKA ANALIZA GENA TP53: NOVA GRANICA U KLINI\u010cKOM LIJE\u010cENJU DIFUZNOG LIMFOMA VELIKIH B-LIMFOCITA (DLBCL) U PASA - MyLav\" \/>\n<meta property=\"og:description\" content=\"Napokon smo stigli: mo\u017eemo po\u010deti s rutinskom procjenom mutacijskog stanja novotvorina kod psa. 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