Overexpression of transcription factors runt-related transcription factor 1 (RUNX1) and nuclear factor, erythroid-derived 2 (NF-E2) was reported in granulocytes of patients with polycythemia vera and other myeloproliferative neoplasms (MPNs).
Interestingly, the level of RUNX1/AML1 and NF-E2 transcripts that are specifically upregulated in acquired polycythemia vera were also upregulated in VHL(P138L) granulocytes.
Silencing NF-E2 in PV patients reverted both aberrancies, demonstrating for the first time that NF-E2 overexpression is both required and sufficient for Epo independence and HSC/CMP expansion in PV.
Although NF-E2 levels correlate with JAK2(V671F) allele burden in some PV cohorts, the molecular mechanism causing aberrant NF-E2 expression has not been described.
They include one patient with PV and +9p with three copies of JAK2 and two patients with MDS and JAK2 relocations: one with NF-E2, while the other patient with a TEL/ETV6 rearrangements also had tetrasomy for JAK2.
Patients with PV who were homozygous or heterozygous for JAK2-V617F exhibited higher levels of expression of the 13 new markers, PRV1, and NF-E2 than patients without JAK2-V617F, whereas ANKRD15 was down-regulated in these patients.