Author/Editor		Vučković, Joško; Pajič, Tadej; Kušec, Rajko; Grat, Mateja; Lorbek, Marjan; Rogulj, Dinko; Pavlič, Rok; Žuran, Ivan
Title		Klinični pomen mutacije V617F JAK2 gena pri kroničnih mieloproliferativnih boleznih - prve izkušnje
Translated title		Clinical meaning of JAK2 V617F mutation in chronic myeloproliferative disorders - the first experience
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 75, št. 10
Publication year		2006
Volume		str. 629-34
Language		slo
Abstract		Background An acquired V617F mutation in the JAK2 gene was found to occur in most patients with polycythaemia vera (PV), and about a half of those with essential thrombocythaemia (ET) and chronic idiopathic myelofibrosis (CIMF). It is the first clonal marker that allows differentiation between reactive thrombocytosis and erythrocytosis from some chronic myeloproliferative disorders (CMPD) - ET, PV and CIMF. It has been proposed that the JAK2 status could also divide ET patients in two distinct subgroups, with mutation positive one showing clinical and laboratory features of PV. Patients and methods Allele-specific PCR for JAK2 mutation was done in 53 patients (35 ET 12 PV and 6 CIMF). In the group of ET patients, some clinical and laboratory features of mutation positive and mutation negative subgroup were compared. Results In general we found V617F mutation in 12/12 (100%) PV, in 15/35 (43%) ET and in 2/6 (33%) CIMF: Mutation positive ET patients had higher haemoglobin (Hb) level and lower platelet counts already at diagnosis. The Hb level had the tendency to increase (observation period 35 months and 2 patients converted to overt PV. In mutation negative patients the Hb level remained equal or even was slightly decreased after observation period (42 months). Up to now there is no statistical difference in leukocyte count, incidence of splenomegaly, antiproliferative drugs demand or disease related complications. Platelet distribution width (PDW) was higher in mutation positive group. Conclusions The fraction of V617F mutation positive patients with CMPD in our work is similar to that found by others. We found this test very useful in differentation of some CMPD cases from the reactive states. Mutation positive ET shares some clinical and laboratory features with PV and overt polycythemic transformation in such patients is possible.
Summary		Izhodišča Pridobljeno mutacijo V627F v genu JAK2 so ugotovili pri večini bolnikov s pravo policitemijo (PP) in pri približno polovici bolnikov z esencialno trombocitemijo (ET) in kronično idiopatsko mielofibrozo (KIMF). To je prvi označevalec za ločevanje reaktivnih motenj krvne slike od omenjenih kroničnih mieloproliferativnih bolezni (KMPB). Začetne raziskave so pokazale, da bi lahko na osnovi mutacije JAK2 razdelili bolnike z ET v dve različni skupini, pri čemer bi skupina s prisotno mutacijo imela nekatere klinične in laboratorijske zrcačilnosti PP. Metode Mutacije V617F smo določali z načinom alelno-specifične verižne reakcije s polimerazo DNK vzorcev 53 bolnikov s KMPB (35 ET, 12 PP in 6 KIMF). Ugotavljali smo razlike v kliničnih in laboratorijskih značilnostih med bolniki z ET in prisotno ali odsotno mutacijo. Rezultati Mutacija V617F je bila prisotna pri 12 od 12 bolnikov s PP (100%), pri 15 od 35 z ET (43%) in pri 2 od 6 (33%) z KIMF. Bolniki z ET, ki so bili za mutacijo pozitivni, so imeli večjo koncentracijo Hb in manjše število trombocitov že ob diagnozi. Pri teh bolnikih je povprečna koncentracija Hb v obdobju spremljanja (35 mesecev) naraščala in pri 2 bolnikih se je bolezen preobrazila v očitno PP. Nasprotno je pri bolnikih brez mutacije koncentracija Hb ostala enaka oz. se je celo rahlo zmanjšala v obdobju spremljanja (42 mesecev). Pri številu levkocitov, pojavnostjo splenomegalije, potrebe po antiproliferativnih zdravilih in prisotnostjo z boleznijo povezanih zapletov med za mutacijo pozitivnimi in negativnimi bolniki z ET nismo zaznali statistično pomembnih razlik. Ugotovili smo statistično pomembno razliko v vrednosti koeficienta variacije volumna trombocitov (KVVT), vrednost, izražena v odstotkih, je bila večja pri bolnikih z ET; katerim smo dokazali mutacijo. (Abstract truncated at 2000 characters)
Descriptors		THROMBOCYTHEMIA, HEMORRHAGIC POLYCYTHEMIA VERA MYELOFIBROSIS MYELOPROLIFERATIVE DISORDERS MUTATION POLYMERASE CHAIN REACTION PLATELET COUNT HEMOGLOBINS