A Proliferation-Inducing Ligand and B-Cell Activating Factor Are Upregulated in Patients with Essential Thrombocythemia

Lukasz Bolkun; Marlena Tynecka; Tomasz Wasiluk; Jaroslaw Piszcz; Aleksandra Starosz; Kamil Grubczak; Marcin Moniuszko; Andrzej Eljaszewicz

doi:10.3390/jcm11164663

A Proliferation-Inducing Ligand and B-Cell Activating Factor Are Upregulated in Patients with Essential Thrombocythemia

J Clin Med. 2022 Aug 9;11(16):4663. doi: 10.3390/jcm11164663.

Authors

Lukasz Bolkun¹, Marlena Tynecka², Tomasz Wasiluk³, Jaroslaw Piszcz¹, Aleksandra Starosz², Kamil Grubczak², Marcin Moniuszko^{2

4}, Andrzej Eljaszewicz²

Affiliations

¹ Department of Haematology, Medical University of Bialystok, ul. M. Skłodowskiej-Curie 24A, 15-276 Bialystok, Poland.
² Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, ul. Waszyngtona 13, 15-269 Bialystok, Poland.
³ Regional Centre for Transfusion Medicine, Bialystok, ul. M. Skłodowskiej-Curie 23, 15-950 Bialystok, Poland.
⁴ Department of Allergology and Internal Medicine, Medical University of Bialystok, ul. M. Skłodowskiej-Curie 24A, 15-276 Bialystok, Poland.

Abstract

A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are cytokines belonging to the tumor necrosis factor family which play an essential role in B-cell maturation, differentiation, and survival. Recent evidence indicates their importance in hematological disorders; however, their function in essential thrombocytosis (ET) pathogenesis remains elusive. Therefore, we aimed to analyze the role of APRIL and BAFF in megakaryocytopoiesis in ET patients. We observed elevated levels of APRIL and BAFF in the plasma of ET patients compared with healthy controls, while no differences were found among patients with different JAK2(V617F) statuses. In addition, APRIL levels were positively associated with the number of platelets and WBC count. In the bone marrow, APRIL but not BAFF levels were higher in ET patients with the JAK2(V617F) mutation; however, JAK2(V617F)-negative patients showed slightly reduced levels of BAFF. In ET patients, we showed that the differentiation of CD34+ progenitor cells towards megakaryocytes induces the expression of both APRIL and BAFF. More importantly, APRIL neutralization significantly reduced platelet production. In conclusion, our data provide evidence that blocking APRIL signaling, which acts as an autocrine growth factor for terminal megakaryocytopoiesis, inhibits platelet production in ET patients, regardless of the status of JAK2(V617F) mutation.

Keywords: APRIL; BAFF; CD34+ progenitor cells; essential thrombocythemia; megakaryocytes; megakaryocytopoiesis.

Grants and funding

This research was supported by the statutory funds of the Medical University of Bialystok. This study was conducted with the use of equipment purchased by the Medical University of Bialystok as part of the RPOWP 2007–2013 funding, Priority I, Axis 1.1, contract no. UDA-RPPD.01.01.00-20-001/15-00 dated 26 June 2015.