ANKRD26基因的持续表达与ANKRD26的生殖细胞突变相关，导致血小板减少症2型（THC2），这是一种与白血病易感性相关的遗传性血小板疾病。一些患者也表现出红细胞增多或/和白细胞增多。利用多个人源性体外模型（细胞系、原发患者细胞和患者来源的iPSCs），我们首次证明ANKRD26在红细胞、巨核细胞和粒细胞分化的早期阶段表达，并且对于祖细胞的增殖是必需的。随着分化的进行，ANKRD26表达逐渐被沉默，以完成三种髓系细胞的细胞成熟。在原发细胞中，承诺祖细胞中的异常ANKRD26表达直接影响三种细胞类型的增殖/分化平衡。我们显示ANKRD26与和调节血细胞产生的三种同源二聚型1细胞因子受体MPL、EPOR和G-CSFR相互作用并且关键调节它们的活动。高于正常水平的ANKRD26防止受体内化，导致增加的信号转导和细胞因子过敏性。这些发现为ANKRD26过表达或其分化过程中缺乏沉默对TCH2患者的髓系血细胞异常负责提供了证据。

Sustained ANKRD26 expression associated with germline ANKRD26 mutations causes Thrombocytopenia 2 (THC2), an inherited platelet disorder associated with leukemia predisposition. Some patients also present with erythrocytosis and/or leukocytosis. Using multiple human-relevant in vitro models (cell lines, primary patient cells and patient-derived iPSCs) we demonstrate for the first time that ANKRD26 is expressed during the early steps of erythroid, megakaryocyte and granulocyte differentiation, and is necessary for progenitor proliferation. As differentiation progresses, ANKRD26 expression is progressively silenced, to complete the cellular maturation of the three myeloid lineages. In primary cells, abnormal ANKRD26 expression in committed progenitors directly impacts the proliferation/differentiation balance for the three cell types. We show that ANKRD26 interacts with and crucially modulates the activity of MPL, EPOR and G-CSFR, three homodimeric type I cytokine receptors that regulate blood cell production. Higher than normal levels of ANKRD26 prevent the receptor internalization that leads to increased signaling and cytokine hypersensitivity. These findings afford evidence how an ANKRD26 overexpression or the absence of its silencing during differentiation is responsible of myeloid blood cell abnormalities in TCH2 patients.