细胞干性特征为静止状态、多能性和长期自我更新能力。对治疗抵抗性白血病干细胞（Leukemic Stem Cells, LSCs）的治疗是慢性髓系白血病（Chronic Myeloid Leukemia, CML）和急性髓系白血病（Acute Myeloid Leukemia, AML）患者复发的主要原因。然而，相同的信号通路经常在LSCs和正常造血干细胞（Hematopoietic Stem Cells, HSCs）中支持干性状态，使得治疗目标为LSCs变得困难。在细胞系和患者样本中，我们发现白细胞介素-33（Interleukin-33, IL-33）信号仅以亚型特异方式促进白血病细胞的干性。IL-33受体ST2在表达BCR/ABL1阳性的CD34+ CML和CD34+ AML细胞以及携带AML1/ETO和DEK/NUP214易位重排或9号染色体缺失[del(9q)]的细胞表面富集。ST2的细胞表面富集水平在其他白血病亚型和HSCs上较低或不存在，与干性、激活Wnt信号和抑制Notch信号相关。IL-33-ST2信号通过激活Wnt、MAPK和NF-κB信号，在培养物和小鼠体内促进AML1/ETO-、DEK/NUP214-和BCR/ABL1阳性的LSCs维持和扩张。Wnt信号及其对Notch途径的抑制上调了编码ST2基因的表达，从而形成了一个细胞自主循环。IL-33-ST2信号促进了CML细胞对酪氨酸激酶抑制剂（Tyrosine Kinase Inhibitor, TKI）尼洛替尼和AML细胞对标准化疗的耐药性。因此，抑制IL-33-ST2信号可能有助于克服这些亚型白血病中化疗或TKI的耐药性，以靶向LSCs。

Cell stemness is characterized by quiescence, pluripotency, and long-term self-renewal capacity. Therapy-resistant leukemic stem cells (LSCs) are the primary cause of relapse in patients with chronic and acute myeloid leukemia (CML and AML). However, the same signaling pathways frequently support stemness in both LSCs and normal hematopoietic stem cells (HSCs), making LSCs difficult to therapeutically target. In cell lines and patient samples, we found that interleukin-33 (IL-33) signaling promoted stemness only in leukemia cells in a subtype-specific manner. The IL-33 receptor ST2 was abundant on the surfaces of CD34+ BCR/ABL1 CML and CD34+ AML cells harboring AML1/ETO and DEK/NUP214 translocations or deletion of chromosome 9q [del(9q)]. The cell surface abundance of ST2, which was lower or absent on other leukemia subtypes and HSCs, correlated with stemness, activated Wnt signaling, and repressed Notch signaling. IL-33-ST2 signaling promoted the maintenance and expansion of AML1/ETO-, DEK/NUP214-, and BCR/ABL1-positive LSCs in culture and in mice by activating Wnt, MAPK, and NF-κB signaling. Wnt signaling and its inhibition of the Notch pathway up-regulated the expression of the gene encoding ST2, thus forming a cell-autonomous loop. IL-33-ST2 signaling promoted the resistance of CML cells to the tyrosine kinase inhibitor (TKI) nilotinib and of AML cells to standard chemotherapy. Thus, inhibiting IL-33-ST2 signaling may target LSCs to overcome resistance to chemotherapy or TKIs in these subtypes of leukemia.