Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells
A leukemic in vitro model produced by transducing Cord Blood derived-hematopoietic CD34+ cells with the MLL-AF9 translocation resulting in the oncogenic fusion protein, is used to assess for sensitivity to Zoledronic acid. These cells are practically immortalized and are of myeloid origin. Prolifera...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844020308641 |
| _version_ | 1818153643230101504 |
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| author | Emanuela Chiarella Bruna Codispoti Annamaria Aloisio Emanuela G. Cosentino Stefania Scicchitano Ylenia Montalcini Daniela Lico Giovanni Morrone Maria Mesuraca Heather M. Bond |
| author_facet | Emanuela Chiarella Bruna Codispoti Annamaria Aloisio Emanuela G. Cosentino Stefania Scicchitano Ylenia Montalcini Daniela Lico Giovanni Morrone Maria Mesuraca Heather M. Bond |
| author_sort | Emanuela Chiarella |
| collection | DOAJ |
| description | A leukemic in vitro model produced by transducing Cord Blood derived-hematopoietic CD34+ cells with the MLL-AF9 translocation resulting in the oncogenic fusion protein, is used to assess for sensitivity to Zoledronic acid. These cells are practically immortalized and are of myeloid origin. Proliferation, clonogenic and stromal co-culture assays showed that the MLL-AF9 cells were considerably more sensitive to Zoledronic acid than normal hematopoietic CD34+ cells or MS-5 stromal cells. The MLL-AF9 cells were notably more inhibited by Zoledronic acid when cultured as colonies in 3 dimensions, requiring cell-cell contacts compared to suspension expansion cultures. This is coherent with the mechanism of action of Zoledronic acid inhibiting farnesyl diphosphate synthase which results in a block in prenylation of GTPases such that their role in the membrane is compromised for cell-cell contacts. Zoledronic acid can be proposed to target the MLL-AF9 leukemic stem cells before they emerge from the hematopoietic niche, which being in proximity to bone osteoclasts where Zoledronic acid is sequestered can be predicted to result in sufficient levels to result in an anti-leukemic action. |
| first_indexed | 2024-12-11T14:13:52Z |
| format | Article |
| id | doaj.art-8ab60b1fe7fe4d05b13b32a686f6a920 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-11T14:13:52Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-8ab60b1fe7fe4d05b13b32a686f6a9202022-12-22T01:03:16ZengElsevierHeliyon2405-84402020-06-0166e04020Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cellsEmanuela Chiarella0Bruna Codispoti1Annamaria Aloisio2Emanuela G. Cosentino3Stefania Scicchitano4Ylenia Montalcini5Daniela Lico6Giovanni Morrone7Maria Mesuraca8Heather M. Bond9Laboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, ItalyLaboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, Italy; Tecnologica Research Institute-Marrelli Health, 88900 Crotone, ItalyLaboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, ItalyLaboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, Italy; Exiris S.r.l., 00128 Roma, ItalyLaboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, ItalyLaboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, ItalyDepartment of Obstetrics & Ginecology, University Magna Græcia, 88100 Catanzaro, ItalyLaboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, ItalyLaboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, Italy; Corresponding author.Laboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, Italy; Corresponding author.A leukemic in vitro model produced by transducing Cord Blood derived-hematopoietic CD34+ cells with the MLL-AF9 translocation resulting in the oncogenic fusion protein, is used to assess for sensitivity to Zoledronic acid. These cells are practically immortalized and are of myeloid origin. Proliferation, clonogenic and stromal co-culture assays showed that the MLL-AF9 cells were considerably more sensitive to Zoledronic acid than normal hematopoietic CD34+ cells or MS-5 stromal cells. The MLL-AF9 cells were notably more inhibited by Zoledronic acid when cultured as colonies in 3 dimensions, requiring cell-cell contacts compared to suspension expansion cultures. This is coherent with the mechanism of action of Zoledronic acid inhibiting farnesyl diphosphate synthase which results in a block in prenylation of GTPases such that their role in the membrane is compromised for cell-cell contacts. Zoledronic acid can be proposed to target the MLL-AF9 leukemic stem cells before they emerge from the hematopoietic niche, which being in proximity to bone osteoclasts where Zoledronic acid is sequestered can be predicted to result in sufficient levels to result in an anti-leukemic action.http://www.sciencedirect.com/science/article/pii/S2405844020308641Biological sciencesCell biologyBiochemistryMolecular biologyCancer researchAcute myeloid leukemia |
| spellingShingle | Emanuela Chiarella Bruna Codispoti Annamaria Aloisio Emanuela G. Cosentino Stefania Scicchitano Ylenia Montalcini Daniela Lico Giovanni Morrone Maria Mesuraca Heather M. Bond Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells Heliyon Biological sciences Cell biology Biochemistry Molecular biology Cancer research Acute myeloid leukemia |
| title | Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells |
| title_full | Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells |
| title_fullStr | Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells |
| title_full_unstemmed | Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells |
| title_short | Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells |
| title_sort | zoledronic acid inhibits the growth of leukemic mll af9 transformed hematopoietic cells |
| topic | Biological sciences Cell biology Biochemistry Molecular biology Cancer research Acute myeloid leukemia |
| url | http://www.sciencedirect.com/science/article/pii/S2405844020308641 |
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