Screening for the JAK2 V617F Mutation in Patients with Hemoglobinopathies

Stephen E. Langabeer1

1 Cancer Molecular Diagnostics, St. James’s Hospital, Dublin, Ireland.

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Stephen E. Langabeer, Cancer Molecular Diagnostics, Trinity Translational Medicine Institute, St. James’s Hospital, Dublin, D08 W9RT, Ireland.
Email: slangabeer@stjames.ie
Telephone: +353 14162413

Received: October 8, 2021
Revised: January 23, 2022
Accepted: January 26, 2022
Published online:February 10, 2022


Some clinical and hematological features of patients with hemoglobinopathies can mimic those a myeloproliferative neoplasm (MPN). Given the shifting epidemiology of hemoglobinopathies, the occurrence of the MPN-associated JAK2 V617F mutation and reasons for testing were audited in hemoglobinopathy patients from Ireland. The JAK2 V617F mutation was not detected in any hemoglobinopathy patients. Given the possible coexistence of an MPN and hemoglobinopathy in the same patient clinical, hematological and morphological features should be carefully considered prior to molecular investigation.

Key words: JAK2 V617F; Myeloproliferative neoplasms; Hemoglobinopathies; Molecular diagnostics

© 2022 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Langabeer SE. Screening for the JAK2 V617F Mutation in Patients with Hemoglobinopathies. International Journal of Hematology Research 2022; 7(1): 195-196 Available from: URL: http://www.ghrnet.org/index.php/ijhr/article/view/3220


The Philadelphia chromosome-negative myeloproliferative neoplasms are molecularly characterised by the acquisition of driver mutations of JAK2, CALR and MPL genes. The specific JAK2 V617F mutation is present in 95% of patients with polycythemia vera and in 50-65% of patients with essential thrombocythemia and primary myelofibrosis with identification a first-line objective in MPN molecular diagnostic algorithms[1]. As some hematological and clinical features of patients with hemoglobinopathies can mimic those of myeloproliferative neoplasms (MPN) such as splenomegaly, increased thrombotic events, an apparent erythrocytosis and occasionally thrombocytosis[2], several studies have screened for the presence of JAK2 V617F in large patient cohorts in areas where hemoglobinopathies are endemic to determine the incidence of a latent MPN[3-6]. Given that the prevalence of hemoglobinopathies such as sickle cell disease and β-thalassemia are increasing in Western Europe[7,8], the value of JAK2 V617F mutation screening was assessed in Irish patients with hemoglobinopathies.

From January 2007 to December 2020 inclusive, a total of 20,139 requests for JAK2 V617F mutation analysis were received at a center for hematological malignancy molecular diagnostics. The JAK2 V617F mutation detection methodology was unchanged throughout the audit period and of these requests, 3,523 (17.5%) were positive. A total of 32 individual patient referrals were identified from hemoglobinopathy patients (sickle cell disease n = 22; beta-thalassemia n = 6; alpha-thalassemia n = 2; unspecified hemoglobinopathy n = 2). Referral clinical details included thrombosis (n = 17), thrombocytosis (n = 5), splenomegaly (n = 2) and not provided (n = 8). The JAK2 V617F was not detected in any of the 32 patient samples.

Acknowledging the small size of the patient population examined it appears that screening for the JAK2 V617F in current Irish hemoglobinopathy patients with clinical and hematological features that mimic an MPN is unwarranted. Given the rare but documented coexistence of a hemoglobinopathy and MPN in the same patient[9-11], assessment of the clinical, hematological and morphological aspects of MPN diagnosis should be considered prior to molecular investigations.


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