最近，一种抑制糖蛋白A重复为主（GARP）介导的TGFβ前肽潜伏相关肽（LAP）释放活性转化生长因子β（TGFβ）的抗体在慢性骨髓增生性肿瘤的小鼠模型中显示出临床前活性。 MPN）。因此，我们研究了 56 名 MPN 患者和 11 名健康供者 (HD) 的外周血淋巴细胞上免疫抑制分子 LAP 和 GARP 的表达。我们发现 MPN 患者的淋巴细胞表达较高水平的 LAP 和 GARP，不同 MPN 诊断之间没有发现明显差异。临床参数对淋巴细胞表达 LAP 和 GARP 的影响表明，与 HD 和 Januskinase2 (JAK2) 突变患者相比，钙网蛋白 (CALR) 突变 MPN 患者的表达增加。与活化血小板 (aPLT) 结合的淋巴细胞比例与 LAP 和 GARP 表达密切相关，表明不是淋巴细胞本身而是 aPLT 导致 MPN 患者淋巴细胞 GARP 和 LAP 表达增加。值得注意的是，JAK2-和 CALRmut 患者之间的血小板计数和抗血栓治疗均未发现差异。血小板基因表达分析未能确定 JAK2- 和 CALRmut 患者之间相关基因表达的差异。© 2024 英国血液学会和 John Wiley

Recently, an antibody which inhibits the glycoprotein A repetitions predominant (GARP)-mediated release of active transforming growth factor beta (TGFβ) from the TGFβ propeptide latency-associated peptide (LAP) showed preclinical activity in a murine model of the chronic myeloproliferative neoplasms (MPN). Consequently, we investigated the expression of the immunosuppressive molecules LAP and GARP on peripheral blood lymphocytes from 56 MPN patients and 11 healthy donors (HD). We found that lymphocytes from patients with MPN express higher levels of LAP and GARP with no strong differences found between the different MPN diagnoses. The impact of clinical parameters on the expression of LAP and GARP by lymphocytes showed that patients with calreticulin (CALR)mut MPN have increased expression compared with HD and patients with the Januskinase2 (JAK2) mutation. The fraction of lymphocytes bound to activated platelets (aPLT) strongly correlate to LAP and GARP expression suggesting that it is not the lymphocytes themselves but aPLT, which confer the increased expression of GARP and LAP on MPN patient lymphocytes. Notably, no differences in neither platelet counts nor anti-thrombotic therapy was identified between patients with JAK2- and CALRmut patients. Analysis of platelet gene expression failed to identify differences in expression of relevant genes between JAK2- and CALRmut patients.© 2024 British Society for Haematology and John Wiley & Sons Ltd.