The JAK2V617F activating mutation has been detected in approximatively 50-60% of patients with essential thrombocythemia (ET), and has been associated with a polycythemia vera (PV)-like phenotype and increased risk of thrombosis. We studied 103 consecutive patients with newly diagnosed ET to investigate the possible correlations between JAK2V617F mutation and allele burden with various clinical and bone marrow (BM) morphological features. JAK2V617F mutation was assessed by direct sequencing of exon 14 from peripheral blood or bone marrow samples. The load of JAK2 mutation was measured by semiquantitative real time PCR allelic discrimination assay. JAK2V617F mutation was detected in 59 cases (57.3%). Patients with mutation presented with higher haemoglobin level, higher haematocrit and lower platelet count than non-mutated patients. BM biopsies of mutated cases showed a higher marrow cellularity, a more pronounced erythroid and myeloid hyperplasia, a higher number of micro- and dysplastic megakaryocytes and a greater amount of dilated sinusoids than non-mutated cases. In the latter group, there was an increased number of total, large, stag-horn and clustered megakaryocytes. The mutation load was directly related to lactate dehydrogenase level, splenomegaly and major thrombotic events. BM biopsies of patients with high allele burden showed myeloid and erythroid dysplasia and a large number of micromegakaryocytes. Furthermore, the three homozygous patients displayed higher numbers of large and aggregated megakaryocytes; the mutation load of the homozygous patients decreased after therapy. Our results confirmed that ET patients with JAK2V617F mutation have a PV-like phenotype, with BM biopsies showing marked morphological changes of the megakaryocyte lineage. Interestingly, a high allele burden seems to be associated with a severe disease. Therefore, JAK2V617F mutation and allele burden may identify distinct clinical and morphological subtypes of ET.
JAK2V617F mutation and allele burden in patients with essential thrombocythemia
PICH, Achille;RIERA, Ludovica;
2011-01-01
Abstract
The JAK2V617F activating mutation has been detected in approximatively 50-60% of patients with essential thrombocythemia (ET), and has been associated with a polycythemia vera (PV)-like phenotype and increased risk of thrombosis. We studied 103 consecutive patients with newly diagnosed ET to investigate the possible correlations between JAK2V617F mutation and allele burden with various clinical and bone marrow (BM) morphological features. JAK2V617F mutation was assessed by direct sequencing of exon 14 from peripheral blood or bone marrow samples. The load of JAK2 mutation was measured by semiquantitative real time PCR allelic discrimination assay. JAK2V617F mutation was detected in 59 cases (57.3%). Patients with mutation presented with higher haemoglobin level, higher haematocrit and lower platelet count than non-mutated patients. BM biopsies of mutated cases showed a higher marrow cellularity, a more pronounced erythroid and myeloid hyperplasia, a higher number of micro- and dysplastic megakaryocytes and a greater amount of dilated sinusoids than non-mutated cases. In the latter group, there was an increased number of total, large, stag-horn and clustered megakaryocytes. The mutation load was directly related to lactate dehydrogenase level, splenomegaly and major thrombotic events. BM biopsies of patients with high allele burden showed myeloid and erythroid dysplasia and a large number of micromegakaryocytes. Furthermore, the three homozygous patients displayed higher numbers of large and aggregated megakaryocytes; the mutation load of the homozygous patients decreased after therapy. Our results confirmed that ET patients with JAK2V617F mutation have a PV-like phenotype, with BM biopsies showing marked morphological changes of the megakaryocyte lineage. Interestingly, a high allele burden seems to be associated with a severe disease. Therefore, JAK2V617F mutation and allele burden may identify distinct clinical and morphological subtypes of ET.
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