Megakaryocytic morphology and clinical parameters in essential thrombocythemia, polycythemia vera, and primary myelofibrosis with and without JAK2 V617F.

CONTEXT: Megakaryocytes are the "hallmark" of Philadelphia chromosome-negative myeloproliferative neoplasms, such as essential thrombocythemia, polycythemia vera, and primary myelofibrosis; their morphology in correlation with Janus kinase 2 (JAK2 V617F) mutation as well as clinical and laboratory parameters remains unknown.

OBJECTIVE: To assess the morphology of megakaryocytes in bone marrow biopsies of patients with and without JAK2 V617F mutation.

DESIGN: Assessment of morphologic features of megakaryocytes in 112 bone marrow biopsies (52 essential thrombocythemia, 38 polycythemia vera, and 22 primary myelofibrosis) and correlation with clinical and laboratory data.

RESULTS: JAK2 V617F mutation was detected in 24 of 52 essential thrombocythemia cases (46.2%), 36 of 38 polycythemia vera cases (97.5%), and 14 of 22 primary myelofibrosis cases (63.6%). By investigating morphometric and clinical parameters using multivariate analysis, we found that higher hemoglobin concentration, higher white blood cell counts, and lower platelet counts were significantly associated with JAK2 V617F. Striking morphologic similarities were found between polycythemia vera JAK2 V617F and primary myelofibrosis JAK2 V617F concerning the localization and cytoplasmic size of megakaryocytes. Although polycythemia vera JAK2 V617F and essential thrombocythemia JAK2 V617F shared similarities in localization, distribution, and amount of megakaryocytes, morphology was different. Megakaryocytic morphology also differed between primary myelofibrosis JAK2 V617F and essential thrombocythemia JAK2 V617F.

CONCLUSION: Our results indicate that primary myelofibrosis JAK2 V617F and polycythemia vera JAK2 V617F share pathogenetic pathways, resulting in morphologically similar megakaryocytes.