Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43
Acute myeloid and lymphoblastic leukemia are poor prognosis hematologic malignancies, which disseminate from the bone marrow into the blood. Blast interactions with selectins expressed by vascular endothelium promote the development of drug resistance and leukostasis. While the role of selectins in...
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MDPI AG
2019-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/9/1253 |
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| author | Caroline Spertini Bénédicte Baïsse Marta Bellone Milica Gikic Tatiana Smirnova Olivier Spertini |
| author_facet | Caroline Spertini Bénédicte Baïsse Marta Bellone Milica Gikic Tatiana Smirnova Olivier Spertini |
| author_sort | Caroline Spertini |
| collection | DOAJ |
| description | Acute myeloid and lymphoblastic leukemia are poor prognosis hematologic malignancies, which disseminate from the bone marrow into the blood. Blast interactions with selectins expressed by vascular endothelium promote the development of drug resistance and leukostasis. While the role of selectins in initiating leukemia blast adhesion is established, our knowledge of the involved selectin ligands is incomplete. Using various primary acute leukemia cells and U937 monoblasts, we identified here functional selectin ligands expressed by myeloblasts and lymphoblasts by performing biochemical studies, expression inhibition by RNA interference and flow adhesion assays on recombinant selectins or selectin ligands immunoadsorbed from primary blast cells. Results demonstrate that P-selectin glycoprotein ligand-1 (PSGL-1) is the major P-selectin ligand on myeloblasts, while it is much less frequently expressed and used by lymphoblasts to interact with endothelial selectins. To roll on E-selectin, myeloblasts use PSGL-1, CD44, and CD43 to various extents and the contribution of these ligands varies strongly among patients. In contrast, the interactions of PSGL-1-deficient lymphoblasts with E-selectin are mainly supported by CD43 and/or CD44. By identifying key selectin ligands expressed by acute leukemia blasts, this study offers novel insight into their involvement in mediating acute leukemia cell adhesion with vascular endothelium and may identify novel therapeutic targets. |
| first_indexed | 2024-03-12T07:38:02Z |
| format | Article |
| id | doaj.art-229088c5428641e0b0ef6961d592635d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:38:02Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-229088c5428641e0b0ef6961d592635d2023-09-02T21:25:29ZengMDPI AGCancers2072-66942019-08-01119125310.3390/cancers11091253cancers11091253Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43Caroline Spertini0Bénédicte Baïsse1Marta Bellone2Milica Gikic3Tatiana Smirnova4Olivier Spertini5Service and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-1011 Lausanne, SwitzerlandService and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-1011 Lausanne, SwitzerlandService and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-1011 Lausanne, SwitzerlandService and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-1011 Lausanne, SwitzerlandService and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-1011 Lausanne, SwitzerlandService and Central Laboratory of Hematology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, CH-1011 Lausanne, SwitzerlandAcute myeloid and lymphoblastic leukemia are poor prognosis hematologic malignancies, which disseminate from the bone marrow into the blood. Blast interactions with selectins expressed by vascular endothelium promote the development of drug resistance and leukostasis. While the role of selectins in initiating leukemia blast adhesion is established, our knowledge of the involved selectin ligands is incomplete. Using various primary acute leukemia cells and U937 monoblasts, we identified here functional selectin ligands expressed by myeloblasts and lymphoblasts by performing biochemical studies, expression inhibition by RNA interference and flow adhesion assays on recombinant selectins or selectin ligands immunoadsorbed from primary blast cells. Results demonstrate that P-selectin glycoprotein ligand-1 (PSGL-1) is the major P-selectin ligand on myeloblasts, while it is much less frequently expressed and used by lymphoblasts to interact with endothelial selectins. To roll on E-selectin, myeloblasts use PSGL-1, CD44, and CD43 to various extents and the contribution of these ligands varies strongly among patients. In contrast, the interactions of PSGL-1-deficient lymphoblasts with E-selectin are mainly supported by CD43 and/or CD44. By identifying key selectin ligands expressed by acute leukemia blasts, this study offers novel insight into their involvement in mediating acute leukemia cell adhesion with vascular endothelium and may identify novel therapeutic targets.https://www.mdpi.com/2072-6694/11/9/1253adhesionacute leukemiaCLAselectinsselectin ligands |
| spellingShingle | Caroline Spertini Bénédicte Baïsse Marta Bellone Milica Gikic Tatiana Smirnova Olivier Spertini Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43 Cancers adhesion acute leukemia CLA selectins selectin ligands |
| title | Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43 |
| title_full | Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43 |
| title_fullStr | Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43 |
| title_full_unstemmed | Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43 |
| title_short | Acute Myeloid and Lymphoblastic Leukemia Cell Interactions with Endothelial Selectins: Critical Role of PSGL-1, CD44 and CD43 |
| title_sort | acute myeloid and lymphoblastic leukemia cell interactions with endothelial selectins critical role of psgl 1 cd44 and cd43 |
| topic | adhesion acute leukemia CLA selectins selectin ligands |
| url | https://www.mdpi.com/2072-6694/11/9/1253 |
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