Bolkun Lukasz, Tynecka Marlena, Wasiluk Tomasz, Piszcz Jaroslaw, Starosz Aleksandra, Grubczak Kamil, Moniuszko Marcin, Eljaszewicz Andrzej
Department of Haematology, Medical University of Bialystok, ul. M. Skłodowskiej-Curie 24A, 15-276 Bialystok, Poland.
Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, ul. Waszyngtona 13, 15-269 Bialystok, Poland.
J Clin Med. 2022 Aug 9;11(16):4663. doi: 10.3390/jcm11164663.
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.
增殖诱导配体（APRIL）和B细胞活化因子（BAFF）是属于肿瘤坏死因子家族的细胞因子，它们在B细胞成熟、分化和存活中发挥着至关重要的作用。最近的证据表明它们在血液系统疾病中的重要性；然而，它们在原发性血小板增多症（ET）发病机制中的作用仍不清楚。因此，我们旨在分析APRIL和BAFF在ET患者巨核细胞生成中的作用。我们观察到，与健康对照相比，ET患者血浆中APRIL和BAFF水平升高，而不同JAK2（V617F）状态的患者之间未发现差异。此外，APRIL水平与血小板数量和白细胞计数呈正相关。在骨髓中，JAK2（V617F）突变的ET患者中APRIL水平较高，而BAFF水平不高；然而，JAK2（V617F）阴性患者的BAFF水平略有降低。在ET患者中，我们发现CD34+祖细胞向巨核细胞的分化诱导了APRIL和BAFF的表达。更重要的是，APRIL中和显著降低了血小板生成。总之，我们的数据提供了证据，即阻断作为终末巨核细胞生成自分泌生长因子的APRIL信号传导，可抑制ET患者的血小板生成，无论JAK2（V617F）突变状态如何。
