Analysis of the V617F Mutation of the JAK2- and the W515 Mutation of the MPL Gene in Patients with Chronic Myeloproliferative Disease (CMPD) Treated in an Outpatient Practice.
Authors: Bojko Peter , Abenhardt Wolfgang , Schnittger Susanne , Haferlach Torsten 
Published: November 2019

Abstract
Background: Patients (pts) treated in a private oncology practice for various subtypes of CMPD were studied for the V617F mutation of the JAK2 gene and the W515 mutation of the MPL gene to compare clinical and hematological data with mutational status.
Results: 51 pts (29 female; 22 male) were screened and 46 pts were analyzed. Median age was 62 ± 13.7 yrs. 27 pts. are diagnosed with Essential Thrombocytemia (ET), 21 pts with Polycythemia vera (PV), 2 pts with Osteomyelofibrosis (CIMF), 2 pts with Chronic Myelo-Monocytic Leukemia (CMML), 1 pt with Hypereosinophilic Syndrome (HES) and 1 pt was not further specified. 3 pts were diagnosed with both ET and PV. 48 pts are currently treated with cytoreductives (hydoxyurea, anagrelide, oral melphalan) phlebotomy or both, and recent irradiation of the spleen, respectively. The mean time from diagnosis to start of treatment was 10.9 ± 23.5 months (range, 0–120 months) for all pts. The median duration of treatment at the time of analysis was 39 months (range, 0–198 months). The median number of treatment regimens is 1 per pt (range, 1–3). Overall, 25 pts (49%) had a JAK2- and 1 pt with ET (2%) a MPL gene mutation. Among pts with PV 12/18 pts (67%; 3 pts not analysed) had mutated JAK2. For ET pts the corresponding number was 15/25 (60%, 2 not analysed). Among the remaining pts, 1 pt with CIMF showed the JAK2 mutation, too. There was no significant difference of the hematocrit at the time of diagnosis in JAK2 mutated and unmutated pts with PV (mean 56.1% ± 7.0% vs 52.7% ± 3.4%, p=0.377). Similar, pts with ET had similar platelet counts at the time of first diagnosis, irrespective of their mutational status (925/nl ± 245/nl vs 790/nl ± 153/nl, p=0.168). The time from first diagnosis to initiation of any specific treatment was 10.1± 25.2 months (range, 0–120 months) and 11.9 ± 21.7 months (range, 0–84 months) for pts with- and without JAK2 mutation, respectively (p=0.795). In summary, our results with 67% JAK2 mutations in PV pts and 60% in ET pts differ from those of other studies (90- and 30%, respectively). In addition to the limited pt number, difficulty in accurate diagnosis of subtypes of MPD, especially in the early course of the disease, could be another explanation. There was no significant difference in clinical relevant parameters as hematocrit, platelet count and time to initiation of any specific treatment in pts with or without mutation of the JAK2 gene. Thus, prognostic relevance of this mutation is still not clear and should be correlated in those pts that undergo transformation to acute leukemia, for example. One potential issue, however, is the development of drugs targeted at this mutated cytoplasmic tyrosine kinase. There was only 1 pt with ET showing the W515 mutation of the MPL gene, which is in accordance with published data, describing mutations in about 1% of pts with ET. No pt with PV could be identified with this mutation, however. Thus, the clinical relevance of this mutation seems to be low in this setting.