Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression

2007 ◽  
Vol 21 (4) ◽  
pp. 1210-1226 ◽  
Author(s):  
Mario Pescatori ◽  
Aldobrando Broccolini ◽  
Carlo Minetti ◽  
Enrico Bertini ◽  
Claudio Bruno ◽  
...  
Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 2156-2164 ◽  
Author(s):  
Laurence Lamant ◽  
Aurélien de Reyniès ◽  
Marie-Michèle Duplantier ◽  
David S. Rickman ◽  
Frédérique Sabourdy ◽  
...  

Abstract With the use of microarray gene-expression profiling, we analyzed a homogeneous series of 32 patients with systemic anaplastic large-cell lymphoma (ALCL) and 5 ALCL cell lines. Unsupervised analysis classified ALCL in 2 clusters, corresponding essentially to morphologic subgroups (ie, common type vs small cell and “mixed” variants) and clinical variables. Patients with a morphologic variant of ALCL had advanced-stage disease. This group included a significant number of patients who experienced early relapse. Supervised analysis showed that ALK+ALCL and ALK− ALCL have different gene-expression profiles, further confirming that they are different entities. Among the most significantly differentially expressed genes between ALK+ and ALK− samples, we found BCL6, PTPN12, CEBPB, and SERPINA1 genes to be overexpressed in ALK+ ALCL. This result was confirmed at the protein level for BCL-6, C/EBPβ and serpinA1 through tissue microarrays. The molecular signature of ALK− ALCL included overexpression of CCR7, CNTFR, IL22, and IL21 genes but did not provide any obvious clues to the molecular mechanism underlying this tumor subtype. Once confirmed on a larger number of patients, the results of the present study could be used for clinical and therapeutic management of patients at the time of diagnosis.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 209-209 ◽  
Author(s):  
Kieron Dunleavy ◽  
Stefania Pittaluga ◽  
John Janik ◽  
Nicole Grant ◽  
Margaret Shovlin ◽  
...  

Abstract PMBL is a distinct clinicopathologic entity characterized by young age, female preponderance, localized disease, prominent sclerosis and CD30+. Gene expression profiling reveals a unique molecular signature, distinct from other DLBCL subtypes, with similarity to classical Hodgkin lymphoma (HL) (J Exp Med 198: 851, 2003). HL is typically CD20 negative whereas PMBL has robust CD20 staining. As with HL, the risk of local failure after anthracycline-based therapy in PMBL has led to routine mediastinal radiation. Given the young median age, female predominance and high cure rates, long-term toxicities from secondary malignancies and coronary artery disease can be life threatening. We prospectively evaluated the role of DA-EPOCH± R without routine radiation in 44 patients with untreated PMBL. The first 18 patients received DA-EPOCH alone and the subsequent 26 received DA-EPOCH+R. DA-EPOCH was administered for 6–8 cycles as described (Blood99: 2685, 2002). Most patients had adverse prognostic features with bulky disease, elevated LDH and extranodal sites, which were balanced among the 2 groups. Patient Characteristics Characteristics All Patients DA-EPOCH DA-EPOCH-R Total Patients 44 18 26 Gender (F/M) 26:18 (1.44) 10:8 (1.25) 19:9 (1.88) Median age, y (range) 34 (12–70) 34 (20–62) 34 (12–70) Median Mass cm (range) 9.8 (3–19.7) 8.4 (5.1–15.7) 10.2 (3–19.7) Bulky mass > 6 cm 34 (83%) 13 (87%) 21 (81%) ECOG PS > 1 4 (9%) 2 (11%) 2 (8%) Stage III or IV 19 (43%) 9 (50%) 10 (38%) LDH > Normal 32 (73%) 14 (78%) 18 (69%) Extranodal sites 25 (57%) 9 (50%) 16 (63%) Pleural effusion 15 (34%) 4 (22%) 11(42%) IHC profiling was similar in both groups and consistent with gene expression profiling of PMBL. Analysis of 40 cases showed CD20+ 40/40 (100%), CD10+ 2/30 (7%), BCL-6+ 21/26 (81%), MUM-1+ 10/24 (42%) and high MIB-1 with median (range) of 82% (54–98). At a median potential follow-up of 9.5 and 4.2 years, EFS and OS are shown below for DA-EPOCH and DA-EPOCH-R, respectively. Rituximab was associated with a significantly improved EFS (p=.038) and OS (p=0.023) by 2-tailed exact log-rank test with caveats associated with any non-randomized comparison. Three patients on DA-EPOCH-R had positive PET and biopsy after treatment. One received radiation (event), one recieved salvage chemotherapy and radiation (event), and one no further treatment after biopsy. DA-EPOCH-R is highly effective in PMBL with OS of 100% and obviated the need for radiation/surgery in 23/26 (88%) patients. Rituximab may significantly improve EFS and OS with DA-EPOCH-based treatment. Accrual continues. Figure Figure


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3275-3275 ◽  
Author(s):  
Ryan van Laar ◽  
Phillip Farmer ◽  
Richard A Bender ◽  
Aga Zielinski ◽  
Kenton Leigh ◽  
...  

Abstract Background: The 70-gene prognostic risk score (MyPRS), originally developed by the University of Arkansas for Medical Sciences, is the most validated genomic assay for prediction of event free and overall survival in asymptomatic, newly diagnosed and relapsed multiple myeloma. Gene expression profiling was performed on CD138+ plasma cells obtained from the bone marrow of individuals with the precursor condition, monoclonal gammopathy of undetermined significance (MGUS), who later progressed to MM. Analysis of the 70 gene risk score vs. the probability of progression to MM requiring therapy was performed. Method and Results: Between 2011 and 2015, MyPRS gene expression profiling of 266 individuals who initially presented with MGUS was performed. The mean length of time between MGUS diagnosis and disease progression or last follow-up was 6.9 years (standard deviation = 4.0 years). The mean length of time between MGUS gene expression profiling and either disease progression or date of last follow-up was 4.8 years (standard deviation = 2.9 years). Disease progression was defined as the development of CRAB criteria or bone marrow plasmacytosis exceeding 60%. 28 patients developed MM requiring therapy within two years of their MGUS GEP. Twelve individuals (5%) were classified as high risk using the previously established threshold for AMG (GEP70 >37.2 = high risk). Four high risk patients (33%) progressed to active MM within 2 years. 24/255 (9%) patients who were classified as low risk progressed to MM within the same length of time. A risk score histogram and binary fitted line plot of risk score vs. probability of progression to MM within 2 years were generated. Conclusion: Performing MyPRS gene expression profiling on patients diagnosed with MGUS provides personalized information on the individuals' risk of progression to MM requiring treatment. While the overall rate of progression is low, approximately 5% of individuals are at higher risk and may benefit from increased monitoring. The 70-gene signature appears useful for identifying high risk behavior in MGUS patients thereby allowing early intervention and possible inclusion in clinical trials. MyPRS provides a risk assessment at a single point in time unlike recently reported metrics (ASCO Abs. # 8004) which measure a change in Hgb and M protein over time, along with bone marrow plasmacytosis, in order to determine the risk of progression. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures van Laar: Signal Genetics, Inc.: Employment. Farmer:University of Arkansas: Employment. Bender:Signal Genetics, Inc.: Employment. Zielinski:Signal Genetics, Inc.: Employment. Leigh:Signal Genetics, Inc.: Employment. Brown:Signal Genetics, Inc.: Employment. Barlogie:Mount Sinai Hospital: Employment. Morgan:Univ of AR for Medical Sciences: Employment; Bristol Meyers: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding.


2017 ◽  
Vol 35 ◽  
pp. 113-115 ◽  
Author(s):  
S. Huet ◽  
B. Tesson ◽  
J. Jais ◽  
A.L. Feldman ◽  
L. Magnano ◽  
...  

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