PB2221 OVEREXPRESSION OF PRV1 GENE IN MYELOID NEOLASMS AND ASSOCIATION WITH OTHER MOELCUALR ABNORMALITIES

Background: The polycythemia rubra vera 1 gene( PRV1 ) gene encodes a cell surface glycoprotein that plays a role in neutrophil activation and transmigration. PRV1 overexpression was found in significant proportion of patients(pts) with BCR‐ABL1 ‐negative myeloproloferative neoplasms(MPN). In the pre‐ JAK2 mutation era testing of PRV1 expression was recommented to differentiate polycythemia vera(PV) and essential thrombocytemia(ET) from secondary erythrocytosis or thombocytosis, respectively. The available data concerning the incidence of PRV1 overexpression, as well as its association with JAK2 gene mutation status is highly variable. Aims: To determine the incidence of PRV1 overexpression in different myeloid neoplasms and its association with other molecular abnormalities. Methods: Overall 167 pts with MPN were included in this study:43 with ET; 30 – PV; 15 ‐ primary myelofibrosis(PMF); 22 ‐ unspecified MPN(uPMN), 53 ‐ chronic myeloid leukemia(CML), including 18 pts at diagnosis and 35 pts on therapy with TKI; 4 pts with chronic myelomonocytic leukemia(CMML). PRV1 expression level was evaluated by reverse‐transcription polymerase chain reaction(RT‐PCR), with co‐amplification of b‐actin RNA as an internal control using total RNA from peripheral blood mononuclear cells. Semi‐quantitative characterization of PRV1 expression was done using 3grade score system: negative (‐): no product of PRV1 amplification; moderately elevated expression (+): PRV1 product with lower intensity than b‐actin product; strong overexpression(++): product of PRV1 amplification with intensity equivalent or higher than that of the b‐actin . To determine the association of PRV1 expression with JAK2 mutation status PRV1 expression was assessed in serial dilutions of homozygous JAK2 V617F RNA in JAK2 wild type RNA. The PRV1 expression was clearly visible in up to 25% JAK2V617F mutation load. All pts were tested for the presence of BCR‐ABL1 , JAK2 V617F, and some cases for CALR and/or MPL W515L/K mutations. Results: Overall, PRV1 overexpression was found in 80.5% of pts with MPN (Table 1): 83.6%(n = 36) in ET; 93.3%(n = 28) in PV; 73.3%(n = 11) in PMF; 61.1%(n = 11) in CML(including 1 pt with co‐expression of BCR‐ABL1 and JAK2 V617F); 95.5%(n = 21) in uMPN. PRV1 overexpression was significantly associated with JAK2 V617F (+) status in BCR‐ABL1 (‐) MPN with frequency of ranging between 73.3% and 95.5%. Interestingly, 3 JAK2 V617F (‐) pts with PMF and PRV1 overexpression were found positive for CALR (n = 2) or MPL (n = 1) mutations. It was found higher prevalence of pts with strong overexpression PRV1 (++) ‐ 67.9%(n = 19) in PV, 71.4%(n = 15) in uMPN, 77.8%(n = 7/9) in CML, with highest value in PMF ‐ 81.8%(n = 9). In contrast, in ET only 58.3%(n = 21) were PRV1 (++). In CMML 1 pt was PRV1 (++) and the second was PRV1 (+). Strong PRV1 expression clearly correlated with JAK2 V617F mutation load: PRV1 (++) was found 24/28(85.7%) of homozygous pts, compared to 20/46 (43.5%) in heterozygous pts and 21/38 (55.3%) in JAK2 V617F(‐) pts. In CML pts on TKI therapy, PRV1 overexpression was found in 6/35 (17.1%) ‐ cases without any molecular response. Summary/Conclusion: PRV1 overexpression was found in a significant proportion of pts with BCR‐ABL1 ‐pos and BCR‐ABL1‐ neg MPN , with highest frequency in PV and lowest in CML. Despite the clear association of PRV1 overexpression and JAK2 V617F status, overexpression was also found in the absence of mutation suggesting alternative underlying mechanisms of activation of PRV1 .