Department of Immunology, University of Manitoba, Winnipeg, Canada.
Research Institute in Oncology and Hematology, CancerCare Manitoba, Winnipeg, Canada.
Br J Haematol. 2019 Jun;185(5):883-887. doi: 10.1111/bjh.15865. Epub 2019 Mar 14.
Within lymphoid tissues, chronic lymphocytic leukaemia (CLL) cells interact with mesenchymal stromal cells (MSC). Inhibitors of phosphoinositide 3-kinase delta (PI3Kδ) cause release of CLL cells from lymphoid tissues into blood. PI3Kδ inhibitors are thought to target only CLL and other immune cells because PI3Kδ expression is restricted to haematopoietic cells. We found that PI3Kδ is unexpectedly expressed in primary MSC derived from CLL patients and healthy donors. PI3Kδ inhibition in MSC using idelalisib or duvelisib significantly reduced their ability to support CLL migration and adhesion. These observations provide the first evidence that PI3Kδ is expressed and functional in CLL MSC.
在淋巴组织中，慢性淋巴细胞白血病 (CLL) 细胞与间充质基质细胞 (MSC) 相互作用。磷酸肌醇 3-激酶 δ (PI3Kδ) 的抑制剂可导致 CLL 细胞从淋巴组织释放到血液中。PI3Kδ 抑制剂被认为仅针对 CLL 和其他免疫细胞，因为 PI3Kδ 的表达仅限于造血细胞。我们发现 PI3Kδ 在源自 CLL 患者和健康供体的原代 MSC 中出人意料地表达。使用idelalisib 或 duvelisib 在 MSC 中抑制 PI3Kδ 可显著降低其支持 CLL 迁移和黏附的能力。这些观察结果首次提供了证据，表明 PI3Kδ 在 CLL MSC 中表达并发挥功能。
