Clinicopathologic characteristics of myeloproliferative neoplasms with JAK2 exon 12 mutation

Leuk Res. 2023 Apr:127:107033. doi: 10.1016/j.leukres.2023.107033. Epub 2023 Feb 8.


The presence of JAK2 exon 12 mutation was included by the 2016 World Health Organization (WHO) Classification as one of the major criteria for diagnosing polycythemia vera (PV). Few studies have evaluated the clinical presentation and bone marrow morphology of these patients and it is unclear if these patients fulfill the newly published criteria of 5th edition WHO or The International Consensus Classification (ICC) criteria for PV. Forty-three patients with JAK2 exon 12 mutations were identified from the files of 7 large academic institutions. Twenty patients had complete CBC and BM data at disease onset. Fourteen patients met the diagnostic criteria for PV and the remaining six patients were diagnosed as MPN-U. At diagnosis, 9/14 patients had normal WBC and platelet counts (isolated erythrocytosis/IE subset); while 5/14 had elevated WBC and/or platelets (polycythemic /P subset). We found that hemoglobin and hematocrit tended to be lower in the polycythemia group. Regardless of presentation (P vs IE), JAK2 deletion commonly occurred in amino acids 541-544 (62 %). MPN-U patients carried JAK2 exon 12 mutation, but did not fulfill the criteria for PV. Half of the patients had hemoglobin/hematocrit below the diagnostic threshold for PV, but showed increased red blood cell count with low mean corpuscular volume (56-60 fL). Three cases lacked evidence of bone marrow hypercellularity. In summary, the future diagnostic criteria for PV may require a modification to account for the variant CBC and BM findings in some patients with JAK2 exon 12 mutation.

Keywords: Bone marrow; Criteria; Diagnosis; Erythrocytosis; JAK2 exon 12; Myeloproliferative; Polycythemia vera.

MeSH terms

  • Bone Marrow / pathology
  • Exons / genetics
  • Humans
  • Janus Kinase 2 / genetics
  • Mutation
  • Myeloproliferative Disorders* / diagnosis
  • Myeloproliferative Disorders* / genetics
  • Myeloproliferative Disorders* / pathology
  • Polycythemia Vera* / diagnosis
  • Polycythemia Vera* / genetics
  • Polycythemia Vera* / pathology
  • Polycythemia* / pathology


  • Janus Kinase 2
  • JAK2 protein, human