Analysis of JAK2V617F Mutation, PRV-1 Overexpression and Endogenous Erythroid Colony (EEC) Formation Show Different Coexpression Patterns among Ph-Negative Chronic Myeloproliferative Disorders.

Introduction. Recently, the JAK2V617F mutation has been reported in the majority of PV patients as well as in a variable percentage of ET and IMF patients. Some authors have reported a high correlation of JAK2 mutation with PRV-1 overexpression and the formation of EECs. In the current study we have analyzed the pattern of positivity of these three biomarkers in a cohort of Ph-negative MPD patients.

Patients and methods. 103 Ph-negative MPD patients (58 ET, 37 PV and 8 IMF) from a single institution were studied. Patients were diagnosed according to the PVSG and Barosi criteria. EEC formation was determined at diagnosis. At the time when PRV-1 and JAK2 mutation were analyzed 29/103 patients were receiving platelet-lowering therapy ± ASA, 26/103 patients only received ASA and 48/103 received no specific treatment. PRV-1 expression was quantified by real-time reverse transcriptase (RT)-PCR in RNA from granulocytes. Analysis of JAK2V617F was performed by direct sequencing using granulocyte RNA. Results. JAK2 mutation was observed in 21/58 ET (36.2%), 30/37 PV (81.1%) and 5/8 IMF (62.5%). PRV-1 was overexpressed in 25/58 ET (43.1%), 35/37 PV (94.6%) and 6/8 IMF (75%) and EECs formation was seen in 31/58 ET (53.4%), 34/37 PV (91.9%) and 6/8 IMF (75%).

All markers were simultaneously positive (group A) in 43/103 patients (41.7%), concurrently negative (group B) in 25/103 patients (24.3%) and both positive and negative markers (group C) were observed in 35/103 patients (34%). In group A, 65% were PV patients, 26% were ET patients and 9 % were IMF patients. In group B, 8% were PV patients, 84% were ET patients and 8 % were IMF patients. In group C, 20% were PV patients, 74% were ET patients and 6 % were IMF patients.

Regarding diagnosis, 76% of PV and 50% of IMF patients belonged to group A, whereas the majority of ET patients (45%) pertained to group C (table). When comparing ET and PV, a significant difference was observed (p<0.001) concerning group distribution.

Conclusion. These results show that, although a good correlation has been observed for the simultaneous expression of these three biomarkers, differences in the pattern of positivity, specially in ET, indicate that not all Ph-negative patients share the same pathogenetic mechanisms and point to other coexisting genetic abnormalities.