HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.

In B-Chronic Lymphocytic Leukemia (B-CLL) kinase Lyn is overexpressed, active, abnormally distributed, and part of a cytosolic complex involving hematopoietic lineage cell-specific protein 1 (HS1). These aberrant properties of Lyn could partially explain leukemic cells' defective apoptosis, dir...

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Autores principales:	Federica Frezzato, Cristina Gattazzo, Veronica Martini, Valentina Trimarco, Antonella Teramo, Samuela Carraro, Anna Cabrelle, Elisa Ave, Monica Facco, Renato Zambello, Elena Tibaldi, Anna Maria Brunati, Gianpietro Semenzato, Livio Trentin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4c11441ec61446e6a96d7f2b910105d5
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spelling	oai:doaj.org-article:4c11441ec61446e6a96d7f2b910105d52021-11-18T07:13:50ZHS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.1932-620310.1371/journal.pone.0039902https://doaj.org/article/4c11441ec61446e6a96d7f2b910105d52012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22768161/?tool=EBIhttps://doaj.org/toc/1932-6203In B-Chronic Lymphocytic Leukemia (B-CLL) kinase Lyn is overexpressed, active, abnormally distributed, and part of a cytosolic complex involving hematopoietic lineage cell-specific protein 1 (HS1). These aberrant properties of Lyn could partially explain leukemic cells' defective apoptosis, directly or through its substrates, for example, HS1 that has been associated to apoptosis in different cell types. To verify the hypothesis of HS1 involvement in Lyn-mediated leukemic cell survival, we investigated HS1 protein in 71 untreated B-CLL patients and 26 healthy controls. We found HS1 overexpressed in leukemic as compared to normal B lymphocytes (1.38±0.54 vs 0.86±0.29, p<0.01), and when HS1 levels were correlated to clinical parameters we found a higher expression of HS1 in poor-prognosis patients. Moreover, HS1 levels significantly decreased in ex vivo leukemic cells of patients responding to a fludarabine-containing regimen. We also observed that HS1 is partially localized in the nucleus of neoplastic B cells. All these data add new information on HS1 study, hypothesizing a pivotal role of HS1 in Lyn-mediated modulation of leukemic cells' survival and focusing, one more time, the attention on the BCR-Lyn axis as a putative target for new therapeutic strategies in this disorder.Federica FrezzatoCristina GattazzoVeronica MartiniValentina TrimarcoAntonella TeramoSamuela CarraroAnna CabrelleElisa AveMonica FaccoRenato ZambelloElena TibaldiAnna Maria BrunatiGianpietro SemenzatoLivio TrentinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39902 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Federica Frezzato Cristina Gattazzo Veronica Martini Valentina Trimarco Antonella Teramo Samuela Carraro Anna Cabrelle Elisa Ave Monica Facco Renato Zambello Elena Tibaldi Anna Maria Brunati Gianpietro Semenzato Livio Trentin HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.
description	In B-Chronic Lymphocytic Leukemia (B-CLL) kinase Lyn is overexpressed, active, abnormally distributed, and part of a cytosolic complex involving hematopoietic lineage cell-specific protein 1 (HS1). These aberrant properties of Lyn could partially explain leukemic cells' defective apoptosis, directly or through its substrates, for example, HS1 that has been associated to apoptosis in different cell types. To verify the hypothesis of HS1 involvement in Lyn-mediated leukemic cell survival, we investigated HS1 protein in 71 untreated B-CLL patients and 26 healthy controls. We found HS1 overexpressed in leukemic as compared to normal B lymphocytes (1.38±0.54 vs 0.86±0.29, p<0.01), and when HS1 levels were correlated to clinical parameters we found a higher expression of HS1 in poor-prognosis patients. Moreover, HS1 levels significantly decreased in ex vivo leukemic cells of patients responding to a fludarabine-containing regimen. We also observed that HS1 is partially localized in the nucleus of neoplastic B cells. All these data add new information on HS1 study, hypothesizing a pivotal role of HS1 in Lyn-mediated modulation of leukemic cells' survival and focusing, one more time, the attention on the BCR-Lyn axis as a putative target for new therapeutic strategies in this disorder.
format	article
author	Federica Frezzato Cristina Gattazzo Veronica Martini Valentina Trimarco Antonella Teramo Samuela Carraro Anna Cabrelle Elisa Ave Monica Facco Renato Zambello Elena Tibaldi Anna Maria Brunati Gianpietro Semenzato Livio Trentin
author_facet	Federica Frezzato Cristina Gattazzo Veronica Martini Valentina Trimarco Antonella Teramo Samuela Carraro Anna Cabrelle Elisa Ave Monica Facco Renato Zambello Elena Tibaldi Anna Maria Brunati Gianpietro Semenzato Livio Trentin
author_sort	Federica Frezzato
title	HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.
title_short	HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.
title_full	HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.
title_fullStr	HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.
title_full_unstemmed	HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.
title_sort	hs1, a lyn kinase substrate, is abnormally expressed in b-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/4c11441ec61446e6a96d7f2b910105d5
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HS1, a Lyn kinase substrate, is abnormally expressed in B-chronic lymphocytic leukemia and correlates with response to fludarabine-based regimen.

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