Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells.
<h4>Background</h4>VLA-4 and CD38 predict a poor clinical outcome in chronic lymphocytic leukemia (CLL). We used CLL samples with discordant VLA-4/CD38 risk to address their individual roles in human bone marrow infiltration (BM), CLL cell homing to murine BM, and in supportive CLL cell-...
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2011
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oai:doaj.org-article:f27c2e873cf34c0db3effd3f5f53862a2021-11-18T06:47:39ZDifferential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells.1932-620310.1371/journal.pone.0023758https://doaj.org/article/f27c2e873cf34c0db3effd3f5f53862a2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21876768/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>VLA-4 and CD38 predict a poor clinical outcome in chronic lymphocytic leukemia (CLL). We used CLL samples with discordant VLA-4/CD38 risk to address their individual roles in human bone marrow infiltration (BM), CLL cell homing to murine BM, and in supportive CLL cell-stromal cell interactions.<h4>Methods</h4>VLA-4, CD38, and Ki-67 expression was measured in CLL cells from peripheral blood (PB) and bone marrow (BM) aspirates. CLL BM infiltration rates, routinely determined by Pathology, were correlated to VLA-4 and CD38 expression. Short-term homing capacity of CLL cells was evaluated by adoptive transfer experiments. CLL cell viability and adhesion in stromal cell co-culture was determined.<h4>Results</h4>About 20% of CLL samples in our cohort displayed discordant VLA-4 and CD38 risk, with either high VLA-4 and low CD38 risk or vice versa. Using particularly such samples, we observed that VLA-4, and not CD38, was responsible for recirculation of CLL cells to murine BM. Human BM infiltration was also significantly higher in patients with high VLA-4 risk but not high CD38 risk. However, both molecules acted as independent prognostic markers. While both VLA-4 and CD38 expression were increased in BM-derived CLL cells, and VLA-4+ and CD38+ subpopulations showed enriched Ki-67 expression, VLA-4 did not contribute to CLL cell protection by stromal cells in vitro.<h4>Conclusions</h4>Our data argue for a prominent role of VLA-4 but not CD38 expression in the homing of CLL cells to BM niches and in human BM infiltration, but only a limited role in their protection by stromal cells.Gabriele BrachtlKarine SahakyanUrsula DenkTamara GirblBeate AlingerSebastian W HofbauerDaniel NeureiterJosefina Piñón HofbauerAlexander EgleRichard GreilTanja Nicole HartmannTanja Nicole HartmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23758 (2011) |
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Medicine R Science Q Gabriele Brachtl Karine Sahakyan Ursula Denk Tamara Girbl Beate Alinger Sebastian W Hofbauer Daniel Neureiter Josefina Piñón Hofbauer Alexander Egle Richard Greil Tanja Nicole Hartmann Tanja Nicole Hartmann Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. |
| description |
<h4>Background</h4>VLA-4 and CD38 predict a poor clinical outcome in chronic lymphocytic leukemia (CLL). We used CLL samples with discordant VLA-4/CD38 risk to address their individual roles in human bone marrow infiltration (BM), CLL cell homing to murine BM, and in supportive CLL cell-stromal cell interactions.<h4>Methods</h4>VLA-4, CD38, and Ki-67 expression was measured in CLL cells from peripheral blood (PB) and bone marrow (BM) aspirates. CLL BM infiltration rates, routinely determined by Pathology, were correlated to VLA-4 and CD38 expression. Short-term homing capacity of CLL cells was evaluated by adoptive transfer experiments. CLL cell viability and adhesion in stromal cell co-culture was determined.<h4>Results</h4>About 20% of CLL samples in our cohort displayed discordant VLA-4 and CD38 risk, with either high VLA-4 and low CD38 risk or vice versa. Using particularly such samples, we observed that VLA-4, and not CD38, was responsible for recirculation of CLL cells to murine BM. Human BM infiltration was also significantly higher in patients with high VLA-4 risk but not high CD38 risk. However, both molecules acted as independent prognostic markers. While both VLA-4 and CD38 expression were increased in BM-derived CLL cells, and VLA-4+ and CD38+ subpopulations showed enriched Ki-67 expression, VLA-4 did not contribute to CLL cell protection by stromal cells in vitro.<h4>Conclusions</h4>Our data argue for a prominent role of VLA-4 but not CD38 expression in the homing of CLL cells to BM niches and in human BM infiltration, but only a limited role in their protection by stromal cells. |
| format |
article |
| author |
Gabriele Brachtl Karine Sahakyan Ursula Denk Tamara Girbl Beate Alinger Sebastian W Hofbauer Daniel Neureiter Josefina Piñón Hofbauer Alexander Egle Richard Greil Tanja Nicole Hartmann Tanja Nicole Hartmann |
| author_facet |
Gabriele Brachtl Karine Sahakyan Ursula Denk Tamara Girbl Beate Alinger Sebastian W Hofbauer Daniel Neureiter Josefina Piñón Hofbauer Alexander Egle Richard Greil Tanja Nicole Hartmann Tanja Nicole Hartmann |
| author_sort |
Gabriele Brachtl |
| title |
Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. |
| title_short |
Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. |
| title_full |
Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. |
| title_fullStr |
Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. |
| title_full_unstemmed |
Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells. |
| title_sort |
differential bone marrow homing capacity of vla-4 and cd38 high expressing chronic lymphocytic leukemia cells. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/f27c2e873cf34c0db3effd3f5f53862a |
| work_keys_str_mv |
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