Detection of Three Different MPLW515 Mutations in 10.1% of All JAK2 V617 Unmutated ET and 9.3% of All JAK2 V617F Unmutated OMF: A Study of 387 Patients.

Recently MPLW515 mutations have been reported in osteomyelofibrosis (OMF) and essential thrombocythemia (ET). To further evaluate this marker for routine diagnostics of CMPD we have analyzed 387 patients (pts) by a melting curve assay and subsequent sequencing of pts with aberrant curves. 97 pts had a diagnosis of ET (79 with unmutated JAK2V617 (V617wt) and 18 with JAK2V617F), 164 had V617wt undefined CMPD with thrombocytosis, 101 had OMF (54 with V617wt and 47 with V617F) and 25 had V617wt/exon12wt polycythemia vera (PV). Overall we detected 3 different mutations in 16 pts: W515L (n=10), W515K (n=5) and a so far undescribed W515S mutation in 1 pt. In 8/97 ET MPLW515 mutations were detected. All 8 pts were V617wt. Thus, the frequency of W515 mutations in V617wt ET was 8/79 (10.1%). In addition, 3/164 (1.8%) CMPD with thrombocytosis were mutated (subsequently classified ET). In OMF MPLW515 mutations were detected in 5 of 54 V617wt pts (9.3%). No MPLW515mut was found in 18 ET and 47 OMF with JAK2V617F and in the 25 V617wt/exon12wt polycythemia vera (PV). In 4 pts the mutation was homozygous (3 W515K, 1 W515L) and all 4 pts were at advanced stage of their disease: 3 OMF 2-6 years (y) after initial diagnosis and 1 ET in transformation 9 y after diagnosis. Mutation/wt ratio in the remaining pts were 10–100% (median: 40%) in ET and 40% in OMF. The female/male ratio in the mutated cases was 9/7. The age was between 30 and 80 y (median 64 y) and thus was in the same range as in V617F mutated ET/OMF (median 65.3 y; n=489) but significantly higher than in V617wt ET/OMF (median 55.6 y; n=410; p