A total of 38 IDH mutations (18 IDH1-R132, 19 IDH2-R140 and 1 IDH2-R172) were detected: 5 (0.8%) ET, 8 (1.9%) PV, 13 (4.2%) PMF, 1 (1%) post-PV/ET MF and 11 (21.6%) blast-phase MPN (P<0.01).
Contrarily, DNA methylation genes (DNMT3A, IDH1, IDH2 and TET2) were mutated most often in PV (0·5) and less frequently in ET (0·23) and PMF (0·20), but without reaching statistical significance.
In polycythemia vera (PV), leukocytosis, abnormal karyotype, phlebotomy requirement on hydroxyurea, increased bone marrow fibrosis, and mutations in ASXL1, SRSF2, and IDH2 were identified as additional adverse prognostic factors.
Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations.
Most recently, ASXL1, SRSF2, and IDH2 mutations have been associated with inferior overall, leukemia-free or fibrosis-free survival in PV; similarly adverse mutations in ET included SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2.
We have studied the mutational status of TET2 (complete coding region), ASXL1 (exon12), IDH1 (R132), IDH2 (R140 and R172), and c-CBL (exons 8 and 9) in 62 MPN patients (52 essential thrombocythemia (ET), five polycythemia vera (PV), and five primary myelofibrosis (PMF)) negative for both JAK2 (V617F and exon 12) and MPL (exon 10) mutations.