Germline MPL Mutations May be a Rare Cause of “Triple-Negative” Thrombocytosis

Hereditary thrombocytosis (HT) are rare inherited disorders with clinical features resembling sporadic essential thrombocythemia. This study included 933 patients with persistent isolated thrombocytosis for whom secondary reactive causes were excluded. Of 933 patients screened, 567 were JAK2-mutated, 255 CALR-mutated, 41 MPL-mutated, 2 double-mutated and 68 triple-negative. Two MPL-mutated patients carried a germline non-canonical mutation located in exon 10: MPL W515* and MPL V501A. One triple-negative patients carried another germline non-canonical MPL mutation located outside exon 10: MPL R102P. As germline MPL mutations may underly HT, we recommend to screen patients with triple-negative isolated thrombocytosis for non-canonical MPL mutations. Although clear evidence concerning treatment of HT is still lacking, individuals with HT should probably not be given a cytoreductive treatment. Thus, a correct diagnosis is pivotal to avoid unnecessary treatments.