Title Splanhničke venske tromboze u kroničnim mijeloproliferativnim neoplazmama Title (english) Splanchnic vein thrombosis in chronic myeloproliferative neoplasms Author Tina Tolić Mentor Rajko Kušec (mentor)Committee member Vlatko Pejša (predsjednik povjerenstva)Committee member Jasenka Markeljević (član povjerenstva)Committee member Rajko Kušec (član povjerenstva)Granter University of Zagreb Defense date and country 2016-07-15, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract UVOD: Kronične mijeloproliferativne neoplazme su skupina klonalnih poremećaja matične stanice koja se odlikuje abnormalnom proliferacijom jedne ili više mijeloidnih loza. PV,ET i PMF zajedničkim imenom nazivaju Philadelphia-negativne kronične mijeloproliferativne neoplazme. Splanhničke venske tromboze predstavljaju najznačajnije komplikacije mijeloproliferativnih neoplazmi, ali i jedini neovisan čimbenik rizika za letalni ishod od ove skupine bolesti. Kod pacijenata sa MPN-om najčešće je zastupljen BCS sa učestalošću od 40,9% , zatim ga slijede TVP sa učestalošću od 31,5%, TVM i TVL su znatno rjeđe od prethodno navedenih. JAK2 V617F mutacija otkrivena 2005. godine ima veliku važnost u dijagnostici MPN. Mutacija JAK2 V617F prisutna je u oko 96% bolesnika s PV-om i u 55-65% bolesnika s ET-om i PMF-om. Iako je utvrđen dijagnostički značaj ove mutacije, njezina uloga u dugoročnom praćenju pacijenata sa MPN još uvijek nije jasna. Pacijente negativne na JAK2 V617F u dijagnostičkom algoritmu potrebno je testirati na rjeđe mutacije poput CARL i MPL.
ISPITANICI I METODE: Istraživanje je provedeno na 7 pacijenata dijagnosticiranih i praćenih u KB Dubrava od 2006.godine nadalje. Pacijenti obuhvaćeni ovom studijom bili su ženskog spola, a medijan dobi je iznosio 56g. Pacijentice su testirane na JAK2V617F mutaciju te im je provedena kvantitativna analiza opterećenosti mutiranim alelom. Ujedno su im analizirani laboratorijski i klinički parametri prisutni u vrijeme dijagnoze.
REZULTATI: Sve pacijentice u trenutku dijagnoze su se prezentirale sa TVP, 5 pacijentica je imalo i TVL, a 1 i TVMS. Analizirani laboratorijski i klinički parametri nisu pokazivali jasnu sliku mijeloproliferacije. Kvantitativnom analizom opterećenosti mutiranim JAK2 V617F alelom rađenom na 4 pacijenta dobili smo nisku opterećenost mutiranim alelom koja se kretala od 4,23%-16,43%. Šest pacijentica je ispunjavalo kriterije za ET, a jedna i za ET i za PMF. Od pridruženih čimbenika rizika za trombozu tri pacijentice su prilikom testiranja na trombofiliju bile pozitivne na PTG20210A, deficit proteina C, i FV Leiden.
RASPRAVA: U skladu sa prethodnim radovima naša studija je dokazala nisku opterećenost mutiranim alelom kod pacijenata sa ET. Također primijetili smo i predominaciju ženskog spola kod pacijenata sa ET koji se prezentiraju sa SVT kao i izostanak jasnih znakova mijeloproliferacije u perifernoj krvi.
ZAKLJUČAK: SVT često predstavljaju prvu manifestaciju podležeće MPN čak i prije nego se u krvnoj slici primijete znakovi mijeloproliferacije. Sukladno tome, pacijente koji se prezentiraju sa SVT, a prethodno smo isključili jetrenu patologiju potrebno je testirati na MPN. Kvantitativna analiza opterećenosti JAK2 V617F alelom mogla bi imati važnu ulogu u određivanju podentiteta MPN. Niska razina opterećenosti mutiranim alelom govori u prilog ET.
Abstract (english) INTRODUCTION: Chronic myeloproliferative diseases are a group of clonal stem cell disorders characterized by abnormal proliferation of one or more myeloid cell lines. PV, ET and PMF are all known under the name of Philadelphia-negative chronic myeloproliferative neoplasms. Splanchnic vein thrombosis is one of the most significant complications of myeloproliferative neoplasms and also the only independent risk factor for a fatal outcome in this group of diseases. Patients with MPNs most commonly develop BCS that occurs in 40,9% of the cases, followed by TVP in 31,5% of the cases with TVL and TVM that are not so commonly present. JAK2 V617F mutation, discovered in 2005, is an important diagnostic tool for the detection of MPNs. This mutation is found in 96% of the patients with PV and in 55-65% of patients with ET and PMF. Although useful in diagnosing patients, the role in long term follow up of the patients with MPNs is still unclear. JAK2 V617F-negative patients must be tested for rare mutations like CARL and MPL.
SUBJECTS AND METHODS: Seven patients, diagnosed and followed up in a clinical hospital Dubrava since 2006, were recruited for this research. All of the subjects in this research were female and the mean age was 56 years. Subjects were tested for JAK2V617F mutations and a quantitative analysis of mutant allele burden was run. Their laboratory and clinical parameters, that were present when they were diagnosed, were also analysed.
RESULTS: Upon being diagnosed with MPNs all of the patients were presented with TVP, 5 of them had also have a TVL, while only one presented with both TVP and TVMS. No clear signs of myeloproliferation were found in an analysed laboratory and clinical data. The results of quantitative analysis of JAK2 V617F allele burden on samples of 4 patients were 4,23%-16,43% which indicates low mutant allele burden. Six of the patients met the criteria for ET and one for ET and PMF. During the testing for thrombophilia three patients were PTG20210A, deficit of protein C and FV Leiden positive, all of them being associated risk factors for thrombosis.
DISCUSSION: Our study showed that there is a low mutant allele burden in patients with ET which is in correlation with other studies. In addition, patients with ET that presented with SVT were mostly female and an absence of overt myeloproliferative signs was found in a peripheral blood.
CONCLUSION: SVT is often presented as a first manifestation of MPN even before notable signs of myeloproliferation in peripheral blood are shown. According to this, patients that present with SVT, and with previously excluded liver disease, should be tested for MPN. Quantitative analysis of JAK2 V617F allele could be an important diagnostic tool for detection of MPN's sub entities. Low mutant allele burden is connected with ET.
Keywords
kronične miijeloproliferativne neoplazme
mutacija
JAK2 V617F
opterećenost mutiranim alelom
Keywords (english)
Chronic myeloproliferative neoplasms
mutation
JAK2 V617F
mutant allele burden
Language croatian URN:NBN urn:nbn:hr:105:273905 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2017-07-03 10:23:17
