在CLL中BCR/Integrin相互作用:具有临床意义的生理残留物
Erika Tissino1, Riccardo Bomben1, Valter Gattei1
1Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Pordenone, Italy.
概括
CD49d表达对布鲁顿细胞上慢性淋巴细胞白血病患者的结果产生负面影响.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
背景情况:
- 非常晚的抗原-4 (VLA-4) 整合蛋白的α链,CD49d,是慢性淋巴细胞白血病 (CLL) 的预后标志物.
- 布鲁顿的氨酸激酶 (BTK) 抑制剂,如易布鲁替尼和阿卡拉布鲁替尼是标准的CLL治疗方法.
- CD49d表达与用BTK抑制剂治疗的CLL患者的预后较差有关.
研究的目的:
- 研究在接受BTK抑制剂治疗的CLL患者中CD49d表达的作用.
- 探索VLA-4激活的机制,尽管BTK抑制.
- 评估CD49d评估对CLL预后分层的有用性.
主要方法:
- 在CLL患者中分析CD49d表达水平.
- 对VLA-4激活通路的评估.
- 评估BTK和酸酸3-激酶 (PI3K) 抑制剂的作用.
主要成果:
- CD49d表达表明,在用易布鲁替尼和阿卡拉布鲁替尼治疗的CLL患者的预后影响是负面的.
- 即使在BTK抑制的情况下,VLA-4仍然通过B细胞受体通路被激活.
- 酸酸3-酶抑制剂可以抑制这种VLA-4激活.
结论:
- CD49d表达是BTK抑制剂治疗CLL患者的显著负面预后因素.
- 针对VLA-4激活通路,可能与PI3K抑制剂,可以克服对BTK抑制剂的耐药性.
- 在BTK抑制剂治疗开始时测量CD49d表达可以完善CLL患者的预后评估.
相关概念视频
01:17Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
01:15Activation of Integrins
3.5K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.5K
01:10Integrins
4.0K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.0K
01:31Immunoglobulin-like Cell Adhesion Molecules
3.3K
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
3.3K
01:24Overview of Cell-Matrix Interactions
7.3K
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
7.3K
01:25Selectins
3.4K
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
3.4K