CONTRIBUTION OF SCREENING FOR JAK 2V617F TO DIAGNOSIS OF CHRONIC MPD

1. CONTRIBUTION OF SCREENING FOR JAK 2V617F TO DIAGNOSIS OF CHRONIC MPD A RETROSPECTIVE STUDY Dr. Miriam Quitt Carmel Hospital

2. Nature434, 1144-1148 (2005)

3. Simultaneous reports on JAK2 mutant in literature

4. Kralovics NEJM352, 1779 (2005)

5. JAK2 V617F MUTANT • JAK2 mutant is a constitutively active tyrosine kinase first described in 2005 • It has been shown that it causes erythropoietin independent erythroid colony growth • In animal models transfection with mutant JAK2 caused erythrocytosis and even myelofibrosis • JAK2 mutant is a hallmark of most polycythemia vera patients and is reported in 40-60%of those with ET and myelofibrosis

6. CLINICAL UTILITY OF JAK2 MUTANT ASSAY IN PV AND ET • JAK2 V617F assay is: • Simple • Inexpensive • Clinical specificity for clonal disease is 100% • Clinical sensitivity for PV 75-90%, for ET 33-50% • Substitutes the complex and expensive diagnostic tests used in the past • WHO proposed presence of JAK2 mutant as a major criteria for PV in presence of erythrocytosis

7. CLINICAL UTILITY OF JAK2 MUTANT ASSAY IN PV AND ET • JAK2 V617F in ET is associated with: • Higher Hb and WBC • Venous thrombosis • Transformation to PV The assay of JAK2 mutant is important for clinical evaluation of patients with MPD

8. AIMS OF THE STUDY • To investigate the frequency of JAK2 V617F mutant in patients with BCR- ABL negative MPD • To find correlation between laboratory findings (leukocytosis, thrombocytosis, presence of JAK2 mutant) and increased incidence of thrombotic complications

9. PATIENTS AND METHODS • 460 patients with suspected /confirmed MPD were referred for test of JAK2 mutant from January 2006- January 2008. • 233 patients that fulfilled the criteria for BCR- ABL negative MPD were included in the study (81 of them were with established dg. prior to 2006). • Retroactive study of electronic files was performed • Clinical and laboratory data at the time of presentation were collected • The presence of complications was investigated

10. BASIC DEMOGRAPHIC AND CLINICAL CHARACTERISTICS

11. PRESENTATION IN ASYMPTOMATIC PATIENTS

12. SYMPTOMS AT PRESENTATION

13. PREVALENCE OF JAK2 MUTANT IN MPD

14. COMPLICATIONS DURING FOLLOW UP

15. INCIDENCE OF THROMBOSIS IN JAK2+ PATIENTS

16. Distribution of patients with thrombosis and JAK2 mutant according the diagnosis

17. Association of JAK2 mutation and thrombocytosis /leukocytosis with thrombosis

18. CONCLUSIONS • In our retrospective study of 233 patients with MPD we found that our patients with PV had a high incidence of JAK2 V617F mutation (89.1%). • The patients with ET had a higher incidence of JAK2 V617F mutation than reported in the literature (74.2%). This may be explained by the fact that many of our patients had a well established diagnosis of MPD several years before the test for JAK2 mutation was included in our routine investigations of MPD.

19. CONCLUSIONS • Because of small number of JAK2V617F negative patients in our study, valid comparison between mutation positive and negative cases was not possible. • In contrary to other reports we did not find increased incidence of thromboembolic episodes in patients with leukocytosis and JAK2 mutant. • We conclude that screening test for JAK2 V617F is a simple and important diagnostic tool that helps to establish the diagnosis in patients with suspected MPD and may provide better prognostic information in the future.

20. Carmel Medical Center L.Gedzun E.Shabad A.Kotler O.Valkovsky M.Ballan N.Lindenfeld A.Cassel I.Lavi Lin Medical Center T.Shusterman Zvulun Medical Center E.Mishchenko Colaborators to this study:

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