Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B<sub>5b </sub>(CYB5B)

<p>Abstract</p> <p>Background</p> <p>We have previously reported a novel constitutively overexpressed 21 kDa protein in Hodgkin Lymphoma (HL) and aggressive Non-Hodgkin Lymphomas (NHL). The objective of the current study was to 1) identify this protein using two indepen...

Full description

Bibliographic Details
Main Authors: Gascoyne Randy D, Karsan Aly, Steidl Christian, Fadlelmola Faisal M, Zhou Minglong, Parker Jeremy, Murphy Derek, Chen Hong, Banerjee Diponkar
Format: Article
Language:English
Published: BMC 2010-01-01
Series:Molecular Cancer
Online Access:http://www.molecular-cancer.com/content/9/1/14
_version_ 1819034528194232320
author Gascoyne Randy D
Karsan Aly
Steidl Christian
Fadlelmola Faisal M
Zhou Minglong
Parker Jeremy
Murphy Derek
Chen Hong
Banerjee Diponkar
author_facet Gascoyne Randy D
Karsan Aly
Steidl Christian
Fadlelmola Faisal M
Zhou Minglong
Parker Jeremy
Murphy Derek
Chen Hong
Banerjee Diponkar
author_sort Gascoyne Randy D
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>We have previously reported a novel constitutively overexpressed 21 kDa protein in Hodgkin Lymphoma (HL) and aggressive Non-Hodgkin Lymphomas (NHL). The objective of the current study was to 1) identify this protein using two independent methods, 2) study the expression of the protein and its encoding mRNA in reactive lymph nodes, normal lymphocytes and CD34+ bone marrow precursor cells, 3) analyse patterns of expression of the protein in tissue microarrays assembled from a large number of diagnostic clinical biopsies from patients with HL, and 4) determine the copy number variation and mutation status of the encoding gene in HL cell lines.</p> <p>Results</p> <p>Peptide sequencing by LC-MS/MS and protein identification by protein array screening identified a single protein, CYB5B. No mutations were detected in the <it>CYB5B </it>gene in HL cell lines. Quantitative PCR showed <it>CYB5B </it>gene expression was increased in HL and NHL cell lines. Array CGH using a submegabase resolution tiling array revealed gains in the <it>CYB5B </it>locus in HL cell lines KMH2 and L428. Membrane expression was seen in Reed-Sternberg cells in clinical biopsies from patients with HL but not in reactive lymph nodes. Bone marrow CD34+ precursor cells were CYB5B negative on the cell surface. RT-PCR assays of RNA extracted from T and B cell enriched fractions obtained from normal peripheral blood mononuclear cells, reactive lymph nodes, tonsils and normal bone marrow samples showed no evidence of increased mRNA levels of <it>CYB5B </it>in comparison to housekeeping gene <it>GAPDH</it>.</p> <p>Conclusions</p> <p>The 21 kDa protein overexpressed in HL and aggressive NHL is identical to CYB5B. <it>CYB5B </it>gene expression is increased in a subset of HL and NHL cell lines tested. This is associated with <it>CYB5B </it>gene amplification in HL cell lines KMH2 and L428. CYB5B may be a potential target for antibody-based therapy of HL and aggressive NHL as although cytoplasmic expression is present in reactive lymphocytes, it is not expressed on the cell surface of non-neoplastic lymphocytes or bone marrow precursor cells.</p>
first_indexed 2024-12-21T07:35:10Z
format Article
id doaj.art-5c2c8abcdfff4f98a5b22c12b906b331
institution Directory Open Access Journal
issn 1476-4598
language English
last_indexed 2024-12-21T07:35:10Z
publishDate 2010-01-01
publisher BMC
record_format Article
series Molecular Cancer
spelling doaj.art-5c2c8abcdfff4f98a5b22c12b906b3312022-12-21T19:11:28ZengBMCMolecular Cancer1476-45982010-01-01911410.1186/1476-4598-9-14Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B<sub>5b </sub>(CYB5B)Gascoyne Randy DKarsan AlySteidl ChristianFadlelmola Faisal MZhou MinglongParker JeremyMurphy DerekChen HongBanerjee Diponkar<p>Abstract</p> <p>Background</p> <p>We have previously reported a novel constitutively overexpressed 21 kDa protein in Hodgkin Lymphoma (HL) and aggressive Non-Hodgkin Lymphomas (NHL). The objective of the current study was to 1) identify this protein using two independent methods, 2) study the expression of the protein and its encoding mRNA in reactive lymph nodes, normal lymphocytes and CD34+ bone marrow precursor cells, 3) analyse patterns of expression of the protein in tissue microarrays assembled from a large number of diagnostic clinical biopsies from patients with HL, and 4) determine the copy number variation and mutation status of the encoding gene in HL cell lines.</p> <p>Results</p> <p>Peptide sequencing by LC-MS/MS and protein identification by protein array screening identified a single protein, CYB5B. No mutations were detected in the <it>CYB5B </it>gene in HL cell lines. Quantitative PCR showed <it>CYB5B </it>gene expression was increased in HL and NHL cell lines. Array CGH using a submegabase resolution tiling array revealed gains in the <it>CYB5B </it>locus in HL cell lines KMH2 and L428. Membrane expression was seen in Reed-Sternberg cells in clinical biopsies from patients with HL but not in reactive lymph nodes. Bone marrow CD34+ precursor cells were CYB5B negative on the cell surface. RT-PCR assays of RNA extracted from T and B cell enriched fractions obtained from normal peripheral blood mononuclear cells, reactive lymph nodes, tonsils and normal bone marrow samples showed no evidence of increased mRNA levels of <it>CYB5B </it>in comparison to housekeeping gene <it>GAPDH</it>.</p> <p>Conclusions</p> <p>The 21 kDa protein overexpressed in HL and aggressive NHL is identical to CYB5B. <it>CYB5B </it>gene expression is increased in a subset of HL and NHL cell lines tested. This is associated with <it>CYB5B </it>gene amplification in HL cell lines KMH2 and L428. CYB5B may be a potential target for antibody-based therapy of HL and aggressive NHL as although cytoplasmic expression is present in reactive lymphocytes, it is not expressed on the cell surface of non-neoplastic lymphocytes or bone marrow precursor cells.</p>http://www.molecular-cancer.com/content/9/1/14
spellingShingle Gascoyne Randy D
Karsan Aly
Steidl Christian
Fadlelmola Faisal M
Zhou Minglong
Parker Jeremy
Murphy Derek
Chen Hong
Banerjee Diponkar
Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B<sub>5b </sub>(CYB5B)
Molecular Cancer
title Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B<sub>5b </sub>(CYB5B)
title_full Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B<sub>5b </sub>(CYB5B)
title_fullStr Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B<sub>5b </sub>(CYB5B)
title_full_unstemmed Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B<sub>5b </sub>(CYB5B)
title_short Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B<sub>5b </sub>(CYB5B)
title_sort constitutively overexpressed 21 kda protein in hodgkin lymphoma and aggressive non hodgkin lymphomas identified as cytochrome b sub 5b sub cyb5b
url http://www.molecular-cancer.com/content/9/1/14
work_keys_str_mv AT gascoynerandyd constitutivelyoverexpressed21kdaproteininhodgkinlymphomaandaggressivenonhodgkinlymphomasidentifiedascytochromebsub5bsubcyb5b
AT karsanaly constitutivelyoverexpressed21kdaproteininhodgkinlymphomaandaggressivenonhodgkinlymphomasidentifiedascytochromebsub5bsubcyb5b
AT steidlchristian constitutivelyoverexpressed21kdaproteininhodgkinlymphomaandaggressivenonhodgkinlymphomasidentifiedascytochromebsub5bsubcyb5b
AT fadlelmolafaisalm constitutivelyoverexpressed21kdaproteininhodgkinlymphomaandaggressivenonhodgkinlymphomasidentifiedascytochromebsub5bsubcyb5b
AT zhouminglong constitutivelyoverexpressed21kdaproteininhodgkinlymphomaandaggressivenonhodgkinlymphomasidentifiedascytochromebsub5bsubcyb5b
AT parkerjeremy constitutivelyoverexpressed21kdaproteininhodgkinlymphomaandaggressivenonhodgkinlymphomasidentifiedascytochromebsub5bsubcyb5b
AT murphyderek constitutivelyoverexpressed21kdaproteininhodgkinlymphomaandaggressivenonhodgkinlymphomasidentifiedascytochromebsub5bsubcyb5b
AT chenhong constitutivelyoverexpressed21kdaproteininhodgkinlymphomaandaggressivenonhodgkinlymphomasidentifiedascytochromebsub5bsubcyb5b
AT banerjeediponkar constitutivelyoverexpressed21kdaproteininhodgkinlymphomaandaggressivenonhodgkinlymphomasidentifiedascytochromebsub5bsubcyb5b