Klinični pomen mutacije JAK2 pri KMPB, analiza bolnikov iz dveh slovenskih regij. Joško Vučković
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1 Klinični pomen mutacije JAK2 pri KMPB, analiza bolnikov iz dveh slovenskih regij Joško Vučković
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3 Prebivalstvo Slovenije po statističnih regijah, 2002 * SLOVENIJA Pomurska Podravska Koroška Savinjska Zasavska Spodnjeposavska Jugovzhodna Slovenija Osrednjeslovenska Gorenjska Notranjsko-kraška Goriška Obalno-kraška izvor: *Statistični urad Republike Slovenije, 2002
4 Kronične mieloproliferativne bolezni v Savinjski in Spodnjeposavski regiji Dijagnoza Broj pacijenata ET 94 PV 45 PMF 30 KML 14 SKUPNO 183
5 Kronične mieloproliferativne bolezni v Celju Dijagnoza Število pacijentov Incidenca / prebivalcev/leto ET 94 3,6 PV 45 1,7 PMF 30 1,1 KML 14 0,5 SKUPNO 183 6,9
6 Tabela 1. Incidenca kroničnih mieloproliferativnih obolenj (/ prebivalcev/leto) Diagnoza Policitemia vera Incidenca (WHO)* Incidenca (SBC,SBB) 1.7 Kronična mieloična levkemija Kronična idiopatska mielofibroza Esencialna trombocitemija *V: Jaffe ES, Lee Harris N, Slein H, Wardiman JW, eds.; Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, WHO Classification of tumours. IARC Press Lyon 2001.
7 Tabela 2. Incidenca (/ prebivalcev/leto) Esencialne trombocitemije (ET) i kronične idiopatske mielofibroze (KIM) u EZ i ZDA Država Ref. ET PMF ZDA Mesa RA et al. (1999) 2,53 1,46 Danska Jensen MK et al. (2000) 0,59 Velika Britanija McNally et al. (1997) ,73-0,40* Švedska Kutti J et al. (2001) 1,5 0,4 Slovenija Podbregar M. Černelč P. (1999) 1,4
8 občina Celje stanovnika
9 Kronične mieloproliferativne bolezni v Celju Dijagnoza Broj pacijenata ET 23 PV 9 PMF 8 KML 0 UKUPNO 40
10 Kronične mieloproliferativne bolezni v Celju ET Dijagnoza Broj pacijenata 23 (16 JAK2+) PV 9 PMF 8 KML 0 UKUPNO 40
11 Kronične mieloproliferativne bolezni v Celju Dijagnoza Število pacijentov Incidenca / prebivalcev/leto ET 23 5,7 PV 9 2,0 PMF 8 2,2 KML 0 0 SKUPNO 40 9,9
12 Število primerov posameznih KMPB na leto
13 KMPB; transformacija in smrtnost ET Umrli Prevalenca December CIMF PV
14 KMPB; prevalenca ET, PV in MF ET Umrli Prevalenca December CIMF 11 26, ,5 PV ,6
15 Tabela 3. Epidemiološke značilnosti kroničnih mijeloproliferativnih bolezni v Sloveniji* Dijagnoza ET PMF PV KML ukupn o Broj pacijenata** Srednja starost pri dg. 64 (19-92) 68(43-84) 65(28-88) 49(35-62) Muških Ženskih Incidencija / /godinu Incidencija u Celju ( stanovnika) 5, *Regija Celjske i Brežičke bolnice- broj stanovnika **U razdoblju )
16 N=94 N=44 N=55 Survival of patients with essential thrombocythemia (ET) polycythemia vera (PV) and primary myelofibrosis (MF)
17 Značilna odkritja na področju KMPB 1951 MPD skupina sorodnih sindromov ki imajo verjetno skupni patogeni vzrok (sir W.D) 1960 Philadelphia chromosom (Ph+) 1973 t(9;22) 1974 EEC brez Epo endogeni potencial rasti 1982 BCR-ABL fusion protein aktivnost TK 1983 potrjena klonalnost PV 2005 mutacija JAK2-V617F aktivnost TK
18 NOT! JustAnotherKinase
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22 Table 2. Established and novel, potential risk factors for thrombosis in patients with polycythemia vera (PV) or essential thrombocythemia (ET). Established risk factors Potential risk factors PV Age 60 y Leukocytosis 41 Previous thrombosis V617F allele 75% 48 ET Age 60 y Leukocytosis 42 Previous thrombosis JAK2V617F mutation 44 Platelets 1500 x 10 9 /L JAK2V617F homozygosity 33
23 Serious vascular complications in patients with ET in relation to JAK2 mutation status complication JAK2 V617F JAK2 WT ET tested 50 patients 41 patients 91 patients ICV TIA AMI TE All complications ( 22%)
24 Serious vascular complications in patients with ET in relation to JAK2 mutation status complication JAK2 V617F JAK2 WT ET tested 50 patients 41 patients 91 patients ICV TIA AMI TE All complications 16 4 P= ( 22%)
25 ZAKLJUČKI Tveganje za nastanek srčnožilnih dogodkov je pri bolnikih z ET in prisotno mutacijo JAK2-V617F znatno večje (p=0.02) kot pri tistih brez mutacije Za preprečevanje srčnožilnih dogodkov pri JAK pozitivnih bolnikih je potreben strožji nadzor dejavnikov tveganja za TE in aterosklerozo in verjetno tudi zgodnejše antiproliferativno zdravljenje.
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27 Tabela 1. Incidenca kroničnih mieloproliferativnih bolezni (/ prebivalcev/leto) * Diagnoza Kronična mieloična levkemija Policitemija vera Kronična idiopatska mielofibroza Esencijalna trombocitemija Incidencija *V: Jaffe ES, Lee Harris N, Slein H, Wardiman JW, eds.; Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, WHO Classification of tumours. IARC Press Lyon 2001.
28 Kronične mieloproliferativne bolezni (KMPB); število prvih dijagnoz ET, PV in PMF ET 107 Umrli Prevalenca December 07 PMF 30 PV 55
29 KMPB; transformacija in smrtnost ET Umrli Prevalenca December CIMF PV
30 Essential thrombocythemia; the rate of transition in polycythemia vera and myelofibrosis Reference Murphy S, et al (PVSG) 1997 ET Patients No Transition to PV No % Tansition to MF No % Follow-up (years) Cervantes F, et al Fenaux P, al Vučković J, et al
31 Kronične mieloproliferativne bolezni WHO klasifikacija Kronična mieloična levkemija (KML) Ph+ kronična neutrofilna levkemija kronična eozinofilna levkemija Policitemija vera (PV) Kronična idiopatska mielofibroza (KIM) Esencialna trombocitemija Neklasificirana kronična mieloproliferativna bolezen
32 Kronične mieloproliferativne bolezni WHO klasifikacija Kronična mieloična levkemija (KML) kronična neutrofilna levkemija kronična eozinofilna levkemija Ph+ Policitemia vera (PV) Hb>185 (165) JAK+ Kronična idiopatska mielofibroza (KIM) Patohist. Esencialna trombocitemija Tr>450x10/9 JAK+ neklasificirana kronična mieloproliferativna bolezen
33 Kronične mieloproliferativne bolezni v Savinjski in Spodnjeposavski regiji Dijagnoza Število pacijentov JAK2+ % ET PV PMF KML 14 SKUPNO 183
34 Epidemiološke značilnosti KMPB v dveh Slovenskih regijah (Savinjska i Spodnjeposavska) J. Vučković
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