[Vascular myeloproliferative neoplasm with normal cell blood count: Exploration and medical management]

J Mal Vasc. 2015 Dec;40(6):350-8. doi: 10.1016/j.jmv.2015.07.002. Epub 2015 Sep 8.
[Article in French]

Abstract

Negative BCR ABL myeloproliferative neoplasm (MPN) such as polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MFP) are clonal hematological malignancies and may lead to a high risk of venous, arterial or microcirculatory thrombosis. Atypical sites of thrombosis can sometimes reveal the neoplasm disorder. Their diagnoses are a major issue because of the propensity to develop acute myeloid leukemia and/or myelofibrosis. The acquired JAK2V617F variant (Janus kinase 2; 9p24) is a prevalent MPN and also a sensitive marker for PV diagnosis (95% positive mutation), but not specific since found in approximately 50% of patients with ET and MFP.

Patient and methods: We present a diagnostic and a therapeutic approach based on one patient with microcirculatory ischemic manifestations in the toes, and who had strictly normal cell blood counts and was positive for JAK2V617F mutation: thrombotic risk factor evaluation; bone marrow biopsy; red cell adhesion assays. These experimental assays are promising for the development of new therapeutics in MPN; they assess red cell adherence to the vascular endothelium after the phosphorylation of Lu/BCAM subsequent to a positive JAK2V617F mutation.

Results: Compared with controls, our patient exhibited increased Lu/BCAM receptor phosphorylation and red blood cell adhesion.

Conclusion: This development may lead to improved care for patients with thrombotic manifestations, normal blood cell counts, and a positive JAK2V617F mutation: multidisciplinary management, including regular hematological monitoring, could lead to the introduction of a cytoreductive treatment.

Keywords: Adhesion assay; JAK2V617F; Mutation JAK2V617F; Tests d’adhérence.

Publication types

  • Case Reports
  • English Abstract
  • Review

MeSH terms

  • Aged
  • Blood Cell Count*
  • Bone Marrow / pathology
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism*
  • Comorbidity
  • Diagnosis, Differential
  • Embolism, Cholesterol / diagnosis
  • Endothelium, Vascular / pathology
  • Erythrocytes / pathology
  • Female
  • France / epidemiology
  • Humans
  • Hydroxyurea / therapeutic use
  • Ischemia / etiology
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Laminin / metabolism
  • Lutheran Blood-Group System / metabolism*
  • Male
  • Microcirculation
  • Mutation, Missense
  • Myeloproliferative Disorders / complications
  • Myeloproliferative Disorders / diagnosis*
  • Myeloproliferative Disorders / drug therapy
  • Myeloproliferative Disorders / epidemiology
  • Myeloproliferative Disorders / genetics
  • Phosphorylation
  • Point Mutation
  • Protein Processing, Post-Translational
  • Risk Factors
  • Smoking / adverse effects
  • Thrombophilia / etiology
  • Toes / blood supply

Substances

  • BCAM protein, human
  • Cell Adhesion Molecules
  • Laminin
  • Lutheran Blood-Group System
  • JAK2 protein, human
  • Janus Kinase 2
  • Hydroxyurea