Mantle cell lymphomas express a distinct genetic signature affecting lymphocyte trafficking and growth regulation as compared with subpopulations of normal human B cells.
(2002) In Cancer Research 62(15). p.4398-4405- Abstract
- Differential gene expression analysis, using high-density microarray chips, demonstrated 300-400 genes to be deregulated in mantle cell lymphomas (MCLs) compared with normal B-cell populations. To investigate the significance of this genetic signature in lymphoma etiology and diagnostics, we selected 90 annotated genes involved in a number of cellular functions for further analysis. Our findings demonstrated a normal gene expression of CCR7, which indicated a normal homing to primary follicles, which was in contrast to other receptors for B-cell trafficking, such as a significant down-regulation for CXCR5 and CCR6, as well as down-regulation of IL4R involved in differentiation. This indicated that the malignant transformation of a normal B... (More)
- Differential gene expression analysis, using high-density microarray chips, demonstrated 300-400 genes to be deregulated in mantle cell lymphomas (MCLs) compared with normal B-cell populations. To investigate the significance of this genetic signature in lymphoma etiology and diagnostics, we selected 90 annotated genes involved in a number of cellular functions for further analysis. Our findings demonstrated a normal gene expression of CCR7, which indicated a normal homing to primary follicles, which was in contrast to other receptors for B-cell trafficking, such as a significant down-regulation for CXCR5 and CCR6, as well as down-regulation of IL4R involved in differentiation. This indicated that the malignant transformation of a normal B cell could have appeared during the transition of a primary follicle to a germinal center, i.e., after an initial B-cell activation. Genes involved in blockage of antiproliferative signals in normal cells were also deregulated, e.g., gene expression of TGFbeta2 and Smad3 was suppressed in MCLs. Furthermore, lymphoproliferative signal pathways were active in MCLs compared with normal B cells, because genes encoding, e.g., IL10Ralpha and IL18 were up-regulated, as were oncogenes like Bcl-2 and MERTK. Genes encoding receptors for different neurotransmitters mediating B-cell stimulation, such as norepinephrine and cannabinoids were also up-regulated, again illustrating deregulation of a complex network of genes involved in growth and differentiation. Furthermore, hierarchical cluster analysis revealed two subpopulations of MCLs, which indicates that despite the homogeneous and strong overexpression of cyclin D1, further subtyping might be possible. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/109703
- author
- Ek, Sara LU ; Högerkorp, Carl-Magnus LU ; Dictor, Michael LU ; Ehinger, Mats LU and Borrebaeck, Carl LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer Research
- volume
- 62
- issue
- 15
- pages
- 4398 - 4405
- publisher
- American Association for Cancer Research Inc.
- external identifiers
-
- wos:000177105600035
- pmid:12154046
- scopus:0036682308
- ISSN
- 1538-7445
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Immunotechnology (011029300), Pathology, (Lund) (013030000)
- id
- fba06611-a0e9-4dba-9ee3-4afd8648bc51 (old id 109703)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12154046&dopt=Abstract
- http://cancerres.aacrjournals.org/cgi/content/full/62/15/4398
- date added to LUP
- 2016-04-01 16:52:38
- date last changed
- 2022-01-28 22:44:56
@article{fba06611-a0e9-4dba-9ee3-4afd8648bc51,
abstract = {{Differential gene expression analysis, using high-density microarray chips, demonstrated 300-400 genes to be deregulated in mantle cell lymphomas (MCLs) compared with normal B-cell populations. To investigate the significance of this genetic signature in lymphoma etiology and diagnostics, we selected 90 annotated genes involved in a number of cellular functions for further analysis. Our findings demonstrated a normal gene expression of CCR7, which indicated a normal homing to primary follicles, which was in contrast to other receptors for B-cell trafficking, such as a significant down-regulation for CXCR5 and CCR6, as well as down-regulation of IL4R involved in differentiation. This indicated that the malignant transformation of a normal B cell could have appeared during the transition of a primary follicle to a germinal center, i.e., after an initial B-cell activation. Genes involved in blockage of antiproliferative signals in normal cells were also deregulated, e.g., gene expression of TGFbeta2 and Smad3 was suppressed in MCLs. Furthermore, lymphoproliferative signal pathways were active in MCLs compared with normal B cells, because genes encoding, e.g., IL10Ralpha and IL18 were up-regulated, as were oncogenes like Bcl-2 and MERTK. Genes encoding receptors for different neurotransmitters mediating B-cell stimulation, such as norepinephrine and cannabinoids were also up-regulated, again illustrating deregulation of a complex network of genes involved in growth and differentiation. Furthermore, hierarchical cluster analysis revealed two subpopulations of MCLs, which indicates that despite the homogeneous and strong overexpression of cyclin D1, further subtyping might be possible.}},
author = {{Ek, Sara and Högerkorp, Carl-Magnus and Dictor, Michael and Ehinger, Mats and Borrebaeck, Carl}},
issn = {{1538-7445}},
language = {{eng}},
number = {{15}},
pages = {{4398--4405}},
publisher = {{American Association for Cancer Research Inc.}},
series = {{Cancer Research}},
title = {{Mantle cell lymphomas express a distinct genetic signature affecting lymphocyte trafficking and growth regulation as compared with subpopulations of normal human B cells.}},
url = {{http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12154046&dopt=Abstract}},
volume = {{62}},
year = {{2002}},
}