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GSE99636
Homo sapiens
21 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Exon 1.0 ST Array [CDF: huex10st_Hs_ENSG_20.0 (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Todays diagnostic tests for multiple myeloma (MM) reflect the criteria of the updated WHO classification based on biomarkers and clinicopathologic heterogeneity. To that end, we propose a new subtyping of myeloma plasma cells (PC) by B-cell subset associated gene signatures (BAGS), from the normal B-cell hierarchy in the bone marrow (BM). To do this, we combined FACS and GEP data from normal BM samples to generate classifiers by BAGS for the PreBI, PreBII, immature (Im), nave (N), memory (M) and PC subsets. The resultant tumor assignments in available clinical datasets exhibited similar BAGS subtype frequencies in four cohorts across 1302 individual cases. The prognostic impact of BAGS was analyzed in patients treated with high dose melphalan as first line therapy in three prospective trials: UAMS, HOVON65/GMMG-HD4 and MRC Myeloma IX with Affymetrix U133 plus 2.0 microarray data available from diagnostic myeloma PC samples. The BAGS subtypes were significantly associated with progression free (PFS) and overall survival (OS) (PFS, P=3.05e06 and OS, P=1.06e11) in a meta-analysis of 926 pts. The major impact was observed within the PreBII and M subtypes conferred with significant inferior prognosis compared to the Im, N and PC subtypes. Cox proportional hazard meta-analysis documented that the BAGS subtypes added significant and independent prognostic information to the TC classification system and ISS staging. BAGS subtype analysis identified transcriptome differences and a number of novel differentially spliced genes. We have identified hierarchal subtype differences in the myeloma plasma cells, with prognostic impact. This observation support an acquired reversible B-cell trait and phenotypic plasticity as a hallmark, also in MM.
Publication Title
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: huex10st_Hs_ENSG_20.0 (huex10st)
Description
Todays diagnostic tests for multiple myeloma (MM) reflect the criteria of the updated WHO classification based on biomarkers and clinicopathologic heterogeneity. To that end, we propose a new subtyping of myeloma plasma cells (PC) by B-cell subset associated gene signatures (BAGS), from the normal B-cell hierarchy in the bone marrow (BM). To do this, we combined FACS and GEP data from normal BM samples to generate classifiers by BAGS for the PreBI, PreBII, immature (Im), nave (N), memory (M) and PC subsets. The resultant tumor assignments in available clinical datasets exhibited similar BAGS subtype frequencies in four cohorts across 1302 individual cases. The prognostic impact of BAGS was analyzed in patients treated with high dose melphalan as first line therapy in three prospective trials: UAMS, HOVON65/GMMG-HD4 and MRC Myeloma IX with Affymetrix U133 plus 2.0 microarray data available from diagnostic myeloma PC samples. The BAGS subtypes were significantly associated with progression free (PFS) and overall survival (OS) (PFS, P=3.05e06 and OS, P=1.06e11) in a meta-analysis of 926 pts. The major impact was observed within the PreBII and M subtypes conferred with significant inferior prognosis compared to the Im, N and PC subtypes. Cox proportional hazard meta-analysis documented that the BAGS subtypes added significant and independent prognostic information to the TC classification system and ISS staging. BAGS subtype analysis identified transcriptome differences and a number of novel differentially spliced genes. We have identified hierarchal subtype differences in the myeloma plasma cells, with prognostic impact. This observation support an acquired reversible B-cell trait and phenotypic plasticity as a hallmark, also in MM.
Publication Title
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. While ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling. DUSP22-rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of genes associated with JAK-STAT3 signaling, a pathway contributing to growth in the majority of ALCLs. Reverse-phase protein array and immunohistochemical studies confirmed the lack of activated STAT3 in DUSP22-rearranged ALCLs. DUSP22-rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes and showed marked DNA hypomethylation by reduced representation bisulfate sequencing and DNA methylation arrays. Pharmacologic DNA demethylation in ALCL cells recapitulated the overexpression of CTAs and other DUSP22 signature genes. Additionally, DUSP22-rearranged ALCLs minimally expressed PD-L1 compared to other ALCLs, but showed high expression of the costimulatory gene CD58 and HLA class II. Taken together, these findings indicate that DUSP22 rearrangements define a molecularly distinct subgroup of ALCLs and that immunogenic cues related to antigenicity, costimulatory molecule expression, and inactivity of the PD-1/PD-L1 immune checkpoint likely contribute to their favorable prognosis. More aggressive ALCLs might be pharmacologically reprogrammed to a DUSP22-like, immunogenic molecular signature through the use of demethylating agents and/or immune checkpoint inhibitors.
Publication Title
Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with <i>DUSP22</i> rearrangements.
Sample Metadata Fields
No sample metadata fields
View Samples