Diagnostic Usefulness of JAK2 Mutation in Manistest or Latent Polycythemia Vera and Secondary Polycythemia.

Backgrounds: The discovery of Janus kinase 2 (JAK2) mutation make it easy to diagnose polycythemia vera (PV) in which the prevalence of this mutation is reported up to 96%. The latent PV is defined in patients who show the lower hemoglobin than WHO criteria at the time of diagnosis without any cause of secondary erythrocytosis; 17~18.5g/dL in male and 15 ~16.5g/dL in female. We investigated the mutational status of JAK2 in polycythemia vera either of latent or manifest type and secondary polycythemia.

Methods : We reviewed the clinical records of 182 patients from 8 centers, who underwent bone marrow (BM) examination with a suspicion of non-BCR/ABL myeloproliferative diseases (nMPD). JAK2 mutation was examined by allele-specific PCR in 110 patients.

Results : The positive rate of JAK2 mutation was 69% of 48 patients with PV, 54% in 41 patients with essential thrombocythemia (ET), 25% of 8 patients with chronic idiopathic myelofibrosis and 100% of 1 patient with unclassifiable MPD. JAK2 mutation was not detected in 7 patients with secondary polycythemia and 5 with reactive thrombocytosis. The number of patients with latent PV was eleven (23%) among the 48 PV patients. Nine of these 11 patients were positive for JAK2 mutation. Finally, sensitivity of JAK2 mutation was 69% (33/48) in all PV, 82% (9/11) in latent PV, and 65% (24/37) in manifest PV. The specificity of JAK2 mutation was 100% for secondary polycythemia. Among the 41 patients with ET, four patient had high hemoglobin met the latent PV criteria. Only one patient among them showed JAK2 mutation. The presence of a JAK2 mutation was closely correlated with the diagnosis of PV (p=0.006), leukocytosis (p=0.000), increased megakaryocytes (p=0.013), and decreased serum EPO (p=0.034) in 98 nMPD patients. In these patients, vascular events before or after the diagnosis and survival were not affected according to JAK2 status during the median follow-up of 25 months (range; 0~211).

Conclusions : The JAK2 mutation help diagnose PV with higher sensitivity in latent PV than manifest PV. This finding can be adopted in the diagnosis of PV in newly visited polycythemic patient whose hemoglobin were under the criteria and condition could be excluded for secondary erythrocytosis. Therefore, JAK2 mutation should be incorporated into the work-up of nMPD including PV for accurate diagnosis. In the meeting, we can present the additional JAK2 data of untested 72 patients.