JAK2V617F mutation and allele burden are associated with distinct clinical and morphological subtypes in patients with essential thrombocythaemia

Aims: To investigate the association between JAK2V617F mutation and allele burden with various clinical and morphological features in bone marrow biopsies (BMB) of patients with essential thrombocythaemia (ET). Methods: 103 consecutive patients with newly diagnosed ET were included in the study. JAK2V617F mutation was assessed by direct sequencing of exon 14 and the load of JAK2 mutation was measured by semiquantitative real time PCR allelic discrimination assay from peripheral blood or bone marrow samples. Results: JAK2V617F mutation was detected in 59 cases (57.3%). Patients with the mutation presented with higher haemoglobin level, haematocrit and lower platelet count than non-mutated patients. BMB of mutated cases showed higher marrow cellularity, a more frequent erythroid and myeloid hyperplasia, a larger number of micro- and dysplastic megakaryocytes and dilated sinusoids. Non-mutated cases displayed an increased number of total, large, “stag-horn” and clustered megakaryocytes. The mutation load was directly related to lactate dehydrogenase (LDH) level, splenomegaly and major thrombotic events; it was associated to a more frequent myeloid and erythroid dysplasia and an increased number of BMB micromegakaryocytes. The three homozygous patients presented with a very large spleen and high LDH level; BMB showed a great number of large and clustered megakaryocytes, and a frequent erythroid and myeloid dysplasia. Conclusions: Our results confirm that ET with JAK2V617F mutation has a polycythaemia vera-like phenotype. JAK2V617 mutational status is strongly associated with BMB morphological changes, mainly of the megakaryocyte lineage. Therefore, JAK2V617F mutation and allele burden may identify distinct clinical and morphological subtypes of ET.