scholarly journals P20. TACI-signalling in multiple myeloma – From the identification as potential therapeutic target by gene expression analysis and functional testing to clinical trials

2006 ◽  
Vol 4 (6) ◽  
pp. 34
Author(s):  
Jérôme Moreaux ◽  
Dirk Hose ◽  
John De Vos ◽  
Jean-François Rossi ◽  
Karène Mahtouk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Expression Analysis ◽  
Therapeutic Target ◽  
Gene Expression Analysis ◽  
Functional Testing ◽  
Potential Therapeutic Target

scholarly journals Prognostic gene expression analysis in a retrospective, multinational cohort of 155 multiple myeloma patients treated outside clinical trials

2021 ◽  
Author(s):  
Yan‐Ting Chen ◽  
Erik T. Valent ◽  
Erik H. Beers ◽  
Rowan Kuiper ◽  
Stefania Oliva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Prognostic Gene

Integration of Gene Mapping and Expression Arrays Identifies Mechanisms by Which Genes Are Dysregulated as a Result of Copy Number Loss and Gain Associated with IgH Translocations in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 395-395 ◽  
Author(s):  
Matthew W. Jenner ◽  
Gonzalez David ◽  
Paola E. Leone ◽  
Brian A. Walker ◽  
David C. Johnson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Expression Analysis ◽  
Copy Number ◽  
Gene Expression Analysis ◽  
Copy Number Change ◽  
Copy Number Loss ◽  
Derivative Chromosome ◽  
Expression Arrays ◽  
Mapping Arrays

Abstract We have previously shown that integration of gene expression and SNP based mapping arrays can identify genes dysregulated as a result of copy number loss and gain in multiple myeloma. Using FISH, it has been possible to identify that gain and loss frequently occurs in association with primary IgH translocations, such as loss of FGFR3 and gain of CCND1 in a proportion of t(4;14) and t(11;14) cases. The aim of this study was to determine the frequency and size of such copy number change associated with IgH translocations and to identify the genes dysregulated as a consequence of these. FISH was performed on CD138 selected plasma cells from 80 newly diagnosed myeloma cases to identify cases with primary IgH translocations. Affymetrix 500K mapping arrays were used to determine copy number change using paired tumor and constitutional DNA and Affymetrix U133 plus 2.0 expression arrays were used to determine global gene expression. Samples were analyzed in dChip and CNAG. Thirty eight of 80 cases (47.5%) had primary IgH translocations: 7 t(4;14), 1 t(6;14), 16 t(11;14), 3 t(14;16), 2 t(14;20) and 9 with an unknown translocation partner. Of 29 cases with a known translocation partner, 11 had gain or loss of all or part of the derivative chromosome. Three of 7 t(4;14) cases had loss of FGFR3 by FISH, confirmed by mapping array as being due to deletion of the derivative 14, with loss of 4p16.3-pter and the remainder of chromosome 14 excluding IgH. The region on 4p commenced at FGFR3 and extended to the telomere. Gene expression analysis showed that there was underexpression of FGFR3 and 4 other genes in the deleted region in the 4p16 deleted cases. In 6 of 16 t(11;14) cases, the translocation was associated with an additional copy of CCND1 by FISH. Mapping arrays revealed in all cases the gain commenced at the presumed translocation breakpoint: in 4 cases there was gain of 11q13.3-qter and in 2 there was gain of a small region of 11q13 only. In most cases there was isolated gain of a variable sized region of 14q32 suggesting a sequence whereby translocation was followed by gain then by deletion of a portion of the derivative chromosome. Gene expression analysis identified 4 genes overexpressed on 11q in t(11;14) cases with 11q gain. In a single t(6;14) case there was a complex rearrangement involving gain of 6p21.1-pter and IgH with loss of the derivative 6, again suggesting translocation followed by gain then loss. In one t(14;16) case there was UPD of 16q except for 16q23-qter with associated gain of IgH alone. This complex pattern suggests a sequence whereby deletion is followed by IgH translocation then by duplication of the untranslocated 16q. This study has shown that loss and gain of translocated regions is a frequent occurrence, present in 11/29 cases with known IgH translocations. Using mapping arrays it is possible to demonstrate that in the majority of cases, the translocation is the initial event, followed by subsequent gain or loss as a later event. We have shown the variable size of these regions and have identified genes dysregulated as a result of the deletions of 4p in t(4;14) cases and gains of 11q in t(11;14) cases. These findings provide evidence of collaborating mechanisms that may be responsible for disease progression in these cases.

Abstract 1873: Gene expression analysis of newly diagnosed Multiple Myeloma (MM) patients carrying amplifiedMDM4and/or deletedp53

2012 ◽  
Author(s):  
Carolina Terragna ◽  
Marina Martello ◽  
Giovanni Martinelli ◽  
Sandra Durante ◽  
Lucia Pantani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Newly Diagnosed

Single-Cell Gene Expression Analysis Identifies Alcam As a Novel Candidate Therapeutic Target in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3915-3915
Author(s):  
Arika Shimura-Nukina ◽  
Yosuke Masamoto ◽  
Yuki Kagoya ◽  
Shunya Arai ◽  
Mineo Kurokawa
Keyword(s):  
Gene Expression ◽  
Cell Surface ◽  
Single Cell ◽  
Expression Analysis ◽  
Therapeutic Target ◽  
Gene Expression Analysis ◽  
Cell Gene Expression ◽  
High Fraction ◽  
Xenotransplantation Model ◽  
Cell Gene

Abstract Acute myeloid leukemia (AML) is the most common acute leukemia in adults, characterized by high rate of relapse even in recent days. AML is organized in a hierarchy of heterogeneous cell populations and relapse is generally attributable to chemoresistant leukemia stem cells (LSCs). Anthracyclins and cytarabine, which cannot eliminate LSCs, have remained the mainstay of AML therapy for almost 40 years and novel drugs targeting LSCs more efficiently are urgently needed. Toward that end, a potential strategy is to identify cell surface markers that can be differentially regulated in LSCs within the bulk of leukemic cells. Here in this study, focusing on heterogeneity of AML cells, we exploited single-cell gene expression analysis to find a novel cell surface antigen differentially expressed in LSCs, which might be missed by analyses as a whole. Firstly, we proposed "single-cell leukemia initiating cell (LIC) score", defined as sum of mRNA expression levels of 15 genes specifically expressed in functionally-determined LICs according to public transcriptome datasets (GSE30375), and graded primary AML samples on a single-cell basis. Single CD34+ CD38- cells (n = 66) and CD34+ CD38+ cells (n = 30) from bone marrow (BM) of two AML patients were analyzed. Single-cell gene expression analysis using Fluidigm technology revealed that within 50 candidate cell surface molecules highly expressed in LICs according to public datasets, expression of 19 genes were positively related to the LIC score. Among them, we focused on ALCAM (Activated Leucocyte Cell Adhesion, CD166), a cell adhesion molecule implicated in tumorigenesis, because survival analyses using public datasets showed that high expression of ALCAM was associated with shorter overall survival in AML. When we examined cell-surface expression of ALCAM in undifferentiated AML cells, ALCAM was highly expressed on CD34+ AML cells compared with CD34+ normal hematopoietic cells. We separated BM cells from AML patients into CD34+ ALCAM high fraction and CD34+ ALCAM low fraction. Colony-forming activities were enriched in CD34+ ALCAM high fraction in vitro (n = 5). And then, we did xenotransplantation model by intravenous injection of human AML BM cells to NSG mice. We show that LICs tended to be enriched within CD34+ ALCAM high fraction in some primary AML samples by using xenotransplantation model. To elucidate whether ALCAM exerts any biological functions and could be a novel therapeutic target in AML, we established human THP-1 AML cells in which expression of ALCAM was silenced by short hairpin RNA (shRNA). Knockdown of ALCAM reduced proliferation and enhanced chemosensitivity of THP-1 cells to cytarabine by curbing genotoxic stress-induced apoptosis in vitro. THP-1 cells expressing shRNA against ALCAM also showed decreased leukomogenic capacity in a xenotransplantation model. When we suppressed activities of ALCAM using a soluble isoform of ALCAM (soluble ALCAM), which binds to ALCAM and inhibits intercellular ALCAM-ALCAM hemophilic interactions, THP-1 cells expressing soluble ALCAM also showed decreased proliferation, enhanced chemosensitivity and decreased leukomogeneic capacity. Furthermore, we transplanted human primary AML cells transduced with a tetracycline-inducible lentiviral construct encoding soluble ALCAM into NSG mice. After engraftment of human cells, expression of soluble ALCAM was induced. BM engraftment of human primary AML cells expressing soluble ALCAM was reduced, which indicated that decreased BM engraftment was not due to impaired homing, but to leukemogenic ability. These findings implicate that LICs with high clonogenic capacity were enriched within CD34+ ALCAM high fraction and ALCAM could be a novel therapeutic target of AML cells. Furthermore, our results also suggests single-cell gene expression analysis and a scoring method such as "LIC score" could be applicable to other hematological malignancies and other cancers to identify and exploit a property of heterogenous cancer cells. Disclosures No relevant conflicts of interest to declare.

Bioinformatic gene expression analysis demonstrates a limited number of multiple myeloma specific therapeutic targets

2021 ◽  
pp. 1-6
Author(s):  
Murari Ramesh ◽  
James Favaloro ◽  
Christian Bryant ◽  
Phoebe Joy Ho ◽  
Edward Abadir
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Therapeutic Targets
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