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.
The most common mutation-cytogenetic combinations in myeloproliferative neoplasm (MPN) were mutations of JAK2 or ASXL1 with del(20q) and were more common in patients with PMF and PV than in patients with ET.
ASXL1 and SRSF2 mutations have been associated with inferior overall, leukemia-free, or fibrosis-free survival in both PV and PMF, and a recent targeted sequencing study has identified additional other adverse mutations in both these disorders, as well as in ET.
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.
We investigated a group of pediatric patients diagnosed either with essential thrombocythemia (ET; N = 9) or polycythemia vera (PV; N = 4) according to WHO criteria (median age = 10 years; range 1.5-15 years) in whom direct sequencing was performed for the existence of genetic alterations in JAK2, MPL, TET2, ASXL1, CBL, IDH1, and IDH2.
Exon 12 of ASXL1 was amplified from neutrophil genomic DNA and bidirectionally sequenced in 77 patients with myelofibrosis (including patients with primary and post-essential thrombocytosis or post-polycythemia myelofibrosis), 42 patients with polycythemia vera, 41 with essential thrombocytosis and 6 with post-myelofibrosis acute myeloid leukemia.