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...
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Format: | Article |
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BMC
2010-01-01
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Series: | Molecular Cancer |
Online Access: | http://www.molecular-cancer.com/content/9/1/14 |
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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> |
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institution | Directory Open Access Journal |
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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 |
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