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Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data

The etiology of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is still obscure as are the processes that enable the progression of MGUS to MM. Understanding the unique vs. shared transcriptomes can potentially elucidate why individuals develop one or the other....

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Autores principales: Aljabban, Jihad, Syed, Sharjeel, Syed, Saad, Rohr, Michael, Mukhtar, Mohamed, Aljabban, Hisham, Cottini, Francesca, Mohammed, Mohammed, Hughes, Tiffany, Gonzalez, Taylor, Panahiazr, Maryam, Hadley, Dexter, Benson, Don
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394915/
https://www.ncbi.nlm.nih.gov/pubmed/37539132
http://dx.doi.org/10.1016/j.heliyon.2023.e17298
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author Aljabban, Jihad
Syed, Sharjeel
Syed, Saad
Rohr, Michael
Mukhtar, Mohamed
Aljabban, Hisham
Cottini, Francesca
Mohammed, Mohammed
Hughes, Tiffany
Gonzalez, Taylor
Panahiazr, Maryam
Hadley, Dexter
Benson, Don
author_facet Aljabban, Jihad
Syed, Sharjeel
Syed, Saad
Rohr, Michael
Mukhtar, Mohamed
Aljabban, Hisham
Cottini, Francesca
Mohammed, Mohammed
Hughes, Tiffany
Gonzalez, Taylor
Panahiazr, Maryam
Hadley, Dexter
Benson, Don
author_sort Aljabban, Jihad
collection PubMed
description The etiology of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is still obscure as are the processes that enable the progression of MGUS to MM. Understanding the unique vs. shared transcriptomes can potentially elucidate why individuals develop one or the other. Furthermore, highlighting key pathways and genes involved in the pathogenesis of MM or the development of MGUS to MM may allow the discovery of novel drug targets and therapies. We employed STARGEO platform to perform three separate meta-analysis to compare MGUS and MM transcriptomes. For these analyses we tagged (1) 101 MGUS patient plasma cells from bone marrow samples and 64 plasma cells from healthy controls (2) 383 MM patient CD138+ cells from bone marrow and the 101 MGUS samples in the first analysis as controls (3) 517 MM patient peripheral blood samples and 97 peripheral blood samples from healthy controls. We then utilized Ingenuity Pathway Analysis (IPA) to analyze the unique genomic signatures within and across these samples. Our study identified genes that may have unique roles in MGUS (GADD45RA and COMMD3), but also newly identified signaling pathways (EIF2, JAK/STAT, and MYC) and gene activity (NRG3, RBFOX2, and PARP15) in MGUS that have previously been shown to be involved in MM suggesting a spectrum of molecular overlap. On the other hand, genes such as DUSP4, RN14, LAMP5, differentially upregulated in MM, may be seen as tipping the scales from benignity to malignancy and could serve as drug targets or novel biomarkers for risk of progression. Furthermore, our analysis of MM identified newly associated gene/pathway activity such as inhibition of Wnt-signaling and defective B cell development. Finally, IPA analysis, suggests the multifactorial, oncogenic qualities of IFNγ signaling in MM may be a unifying pathway for these diverse mechanisms and prompts the need for further studies.
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spelling pubmed-103949152023-08-03 Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data Aljabban, Jihad Syed, Sharjeel Syed, Saad Rohr, Michael Mukhtar, Mohamed Aljabban, Hisham Cottini, Francesca Mohammed, Mohammed Hughes, Tiffany Gonzalez, Taylor Panahiazr, Maryam Hadley, Dexter Benson, Don Heliyon Research Article The etiology of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is still obscure as are the processes that enable the progression of MGUS to MM. Understanding the unique vs. shared transcriptomes can potentially elucidate why individuals develop one or the other. Furthermore, highlighting key pathways and genes involved in the pathogenesis of MM or the development of MGUS to MM may allow the discovery of novel drug targets and therapies. We employed STARGEO platform to perform three separate meta-analysis to compare MGUS and MM transcriptomes. For these analyses we tagged (1) 101 MGUS patient plasma cells from bone marrow samples and 64 plasma cells from healthy controls (2) 383 MM patient CD138+ cells from bone marrow and the 101 MGUS samples in the first analysis as controls (3) 517 MM patient peripheral blood samples and 97 peripheral blood samples from healthy controls. We then utilized Ingenuity Pathway Analysis (IPA) to analyze the unique genomic signatures within and across these samples. Our study identified genes that may have unique roles in MGUS (GADD45RA and COMMD3), but also newly identified signaling pathways (EIF2, JAK/STAT, and MYC) and gene activity (NRG3, RBFOX2, and PARP15) in MGUS that have previously been shown to be involved in MM suggesting a spectrum of molecular overlap. On the other hand, genes such as DUSP4, RN14, LAMP5, differentially upregulated in MM, may be seen as tipping the scales from benignity to malignancy and could serve as drug targets or novel biomarkers for risk of progression. Furthermore, our analysis of MM identified newly associated gene/pathway activity such as inhibition of Wnt-signaling and defective B cell development. Finally, IPA analysis, suggests the multifactorial, oncogenic qualities of IFNγ signaling in MM may be a unifying pathway for these diverse mechanisms and prompts the need for further studies. Elsevier 2023-06-28 /pmc/articles/PMC10394915/ /pubmed/37539132 http://dx.doi.org/10.1016/j.heliyon.2023.e17298 Text en © 2023 Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Aljabban, Jihad
Syed, Sharjeel
Syed, Saad
Rohr, Michael
Mukhtar, Mohamed
Aljabban, Hisham
Cottini, Francesca
Mohammed, Mohammed
Hughes, Tiffany
Gonzalez, Taylor
Panahiazr, Maryam
Hadley, Dexter
Benson, Don
Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data
title Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data
title_full Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data
title_fullStr Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data
title_full_unstemmed Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data
title_short Characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of GEO data
title_sort characterization of monoclonal gammopathy of undetermined significance progression to multiple myeloma through meta-analysis of geo data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394915/
https://www.ncbi.nlm.nih.gov/pubmed/37539132
http://dx.doi.org/10.1016/j.heliyon.2023.e17298
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