Cargando…

The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia

Precursor-B cell receptor (pre-BCR) signaling represents a crucial checkpoint at the pre-B cell stage. Aberrant pre-BCR signaling is considered as a key factor for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) development. BCP-ALL are believed to be arrested at the pre-BCR checkpoint indep...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Dongfeng, Zheng, Junxiong, Gerasimcik, Natalija, Lagerstedt, Kristina, Sjögren, Helene, Abrahamsson, Jonas, Fogelstrand, Linda, Mårtensson, Inga-Lill
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017602/
https://www.ncbi.nlm.nih.gov/pubmed/27611867
http://dx.doi.org/10.1371/journal.pone.0162638
_version_ 1782452778320265216
author Chen, Dongfeng
Zheng, Junxiong
Gerasimcik, Natalija
Lagerstedt, Kristina
Sjögren, Helene
Abrahamsson, Jonas
Fogelstrand, Linda
Mårtensson, Inga-Lill
author_facet Chen, Dongfeng
Zheng, Junxiong
Gerasimcik, Natalija
Lagerstedt, Kristina
Sjögren, Helene
Abrahamsson, Jonas
Fogelstrand, Linda
Mårtensson, Inga-Lill
author_sort Chen, Dongfeng
collection PubMed
description Precursor-B cell receptor (pre-BCR) signaling represents a crucial checkpoint at the pre-B cell stage. Aberrant pre-BCR signaling is considered as a key factor for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) development. BCP-ALL are believed to be arrested at the pre-BCR checkpoint independent of pre-BCR expression. However, the cellular stage at which BCP-ALL are arrested and whether this relates to expression of the pre-BCR components (IGHM, IGLL1 and VPREB1) is still unclear. Here, we show differential protein expression and copy number variation (CNV) patterns of the pre-BCR components in pediatric BCP-ALL. Moreover, analyzing six BCP-ALL data sets (n = 733), we demonstrate that TCF3-PBX1 ALL express high levels of IGHM, IGLL1 and VPREB1, and are arrested at the pre-B stage. By contrast, ETV6-RUNX1 ALL express low levels of IGHM or VPREB1, and are arrested at the pro-B stage. Irrespective of subtype, ALL with high levels of IGHM, IGLL1 and VPREB1 are arrested at the pre-B stage and correlate with good prognosis in high-risk pediatric BCP-ALL (n = 207). Our findings suggest that BCP-ALL are arrested at different cellular stages, which relates to the expression pattern of the pre-BCR components that could serve as prognostic markers for high-risk pediatric BCP-ALL patients.
format Online
Article
Text
id pubmed-5017602
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-50176022016-09-27 The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia Chen, Dongfeng Zheng, Junxiong Gerasimcik, Natalija Lagerstedt, Kristina Sjögren, Helene Abrahamsson, Jonas Fogelstrand, Linda Mårtensson, Inga-Lill PLoS One Research Article Precursor-B cell receptor (pre-BCR) signaling represents a crucial checkpoint at the pre-B cell stage. Aberrant pre-BCR signaling is considered as a key factor for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) development. BCP-ALL are believed to be arrested at the pre-BCR checkpoint independent of pre-BCR expression. However, the cellular stage at which BCP-ALL are arrested and whether this relates to expression of the pre-BCR components (IGHM, IGLL1 and VPREB1) is still unclear. Here, we show differential protein expression and copy number variation (CNV) patterns of the pre-BCR components in pediatric BCP-ALL. Moreover, analyzing six BCP-ALL data sets (n = 733), we demonstrate that TCF3-PBX1 ALL express high levels of IGHM, IGLL1 and VPREB1, and are arrested at the pre-B stage. By contrast, ETV6-RUNX1 ALL express low levels of IGHM or VPREB1, and are arrested at the pro-B stage. Irrespective of subtype, ALL with high levels of IGHM, IGLL1 and VPREB1 are arrested at the pre-B stage and correlate with good prognosis in high-risk pediatric BCP-ALL (n = 207). Our findings suggest that BCP-ALL are arrested at different cellular stages, which relates to the expression pattern of the pre-BCR components that could serve as prognostic markers for high-risk pediatric BCP-ALL patients. Public Library of Science 2016-09-09 /pmc/articles/PMC5017602/ /pubmed/27611867 http://dx.doi.org/10.1371/journal.pone.0162638 Text en © 2016 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chen, Dongfeng
Zheng, Junxiong
Gerasimcik, Natalija
Lagerstedt, Kristina
Sjögren, Helene
Abrahamsson, Jonas
Fogelstrand, Linda
Mårtensson, Inga-Lill
The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia
title The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia
title_full The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia
title_fullStr The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia
title_full_unstemmed The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia
title_short The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia
title_sort expression pattern of the pre-b cell receptor components correlates with cellular stage and clinical outcome in acute lymphoblastic leukemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017602/
https://www.ncbi.nlm.nih.gov/pubmed/27611867
http://dx.doi.org/10.1371/journal.pone.0162638
work_keys_str_mv AT chendongfeng theexpressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT zhengjunxiong theexpressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT gerasimciknatalija theexpressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT lagerstedtkristina theexpressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT sjogrenhelene theexpressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT abrahamssonjonas theexpressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT fogelstrandlinda theexpressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT martenssoningalill theexpressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT chendongfeng expressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT zhengjunxiong expressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT gerasimciknatalija expressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT lagerstedtkristina expressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT sjogrenhelene expressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT abrahamssonjonas expressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT fogelstrandlinda expressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia
AT martenssoningalill expressionpatternoftheprebcellreceptorcomponentscorrelateswithcellularstageandclinicaloutcomeinacutelymphoblasticleukemia