scholarly journals Notch1 switches progenitor competence in inducing medulloblastoma

2020 ◽  
Author(s):  
Claudio Ballabio ◽  
Matteo Gianesello ◽  
Chiara Lago ◽  
Konstantin Okonechnikov ◽  
Marica Anderle ◽  
...  
Keyword(s):  
Brain Cancer ◽  
Poor Prognosis ◽  
Cell Of Origin ◽  
Pathway Activity ◽  
Mouse Cerebellum ◽  
Cells Of Origin ◽  
Cancer Subtype ◽  
Prognosis Group ◽  
Group 3 ◽  
Cellular Identity

SummaryThe identity of the cell of origin is a key determinant of cancer subtype, progression and prognosis. Group 3 Medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and unknown cell of origin. We overexpressed the Group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b+ cells are competent to initiate Group 3 MB, while Math1+, Sox2+ or Ascl1+ cells are not. We noted that S100b+ cells have higher levels of Notch1 pathway activity compared to Math1+ cells. Interestingly, we found that additional activation of Notch1 in Math1+ cells was sufficient to induce Group 3 MB upon MYC/Gfi1 expression. Taken together, our data suggest that the MB cell of origin competence depends on the cellular identity, which relies on Notch1 activity.Graphical Abstract

scholarly journals Notch1 switches progenitor competence in inducing medulloblastoma

2021 ◽  
Vol 7 (26) ◽  
pp. eabd2781
Author(s):  
Claudio Ballabio ◽  
Matteo Gianesello ◽  
Chiara Lago ◽  
Konstantin Okonechnikov ◽  
Marica Anderle ◽  
...  
Keyword(s):  
Brain Cancer ◽  
Poor Prognosis ◽  
Critical Role ◽  
Cell Of Origin ◽  
Pathway Activity ◽  
Mouse Cerebellum ◽  
Cells Of Origin ◽  
Cancer Subtype ◽  
Prognosis Group ◽  
Group 3

The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b+ cells are competent to initiate group 3 MB, and we observed that S100b+ cells have higher levels of Notch1 pathway activity compared to Math1+ cells. We found that additional activation of Notch1 in Math1+ and Sox2+ cells was sufficient to induce group 3 MB upon MYC/Gfi1 expression. Together, our data suggest that the Notch1 pathway plays a critical role in group 3 MB initiation.

scholarly journals Research on the Correlation of Serum PCT and Plasma GSN Levels with the Prognosis of Urosepsis Patients

2020 ◽  
Vol 36 (5) ◽  
Author(s):  
Na Cui ◽  
Zhanbiao Yu ◽  
Zhi Chen ◽  
Ning Chen
Keyword(s):  
Poor Prognosis ◽  
Original Work ◽  
Protective Factor ◽  
Good Prognosis ◽  
Control Group ◽  
Creative Commons ◽  
The Poor ◽  
Prognosis Group ◽  
Good Prognosis Group ◽  
Open Access Article

Objective: To explore the correlation of procalcitonin (PCT) and gelsolin (GSN) with the prognosis of urosepsis patients. Method: The data of 71 urosepsis patients from March 2015 to April 2019 who were admitted to and treated in Affiliated Hospital of Hebei University were analyzed and compared with those of 92 healthy persons. Serum PCT and plasma GSN levels at different times after treatment were detected. According to prognosis, patients were classified into the good prognosis group or the poor prognosis group. The serum PCT and plasma GSN levels of both groups were compared. Result: The serum PCT level of the urosepsis group on the 1st, 3rd, 5th and 7th days was obviously higher than that of the control group (P<0.05). The plasma GSN levels of the urosepsis group on the 1st, 3rd, 5th and 7th days were obviously lower than those of the control group (P<0.05).The serum PCT level of the poor prognosis group on the 1st, 3rd, 5th and 7th days was obviously higher than that of the good prognosis group (P<0.05). The plasma GSN level of the poor prognosis group on the 1st, 3rd, 5th and 7th days was obviously lower than that of the good prognosis group (P<0.05). PCT was an independent risk factor influencing the prognosis of urosepsis patients and that GSN was a protective factor (P<0.05). Conclusion: The serum PCT and plasma GSN levels can accurately predict the severity and prognosis of urosepsis patients and reflect the disease state of early urosepsis patients. High PCT levels and low GSN levels indicate poor prognosis, and clinicians should consider these values. doi: https://doi.org/10.12669/pjms.36.5.2143 How to cite this:Cui N, Yu Z, Chen Z, Chen N. Research on the Correlation of Serum PCT and Plasma GSN Levels with the Prognosis of Urosepsis Patients. Pak J Med Sci. 2020;36(5):---------. doi: https://doi.org/10.12669/pjms.36.5.2143 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals The prognosis prediction significance of Hounsfield unit value for stroke patients treated by intravenous thrombolysis

2020 ◽  
Author(s):  
Zhengqi Zhu ◽  
Ru Zhang ◽  
Kaixuan Ren ◽  
Ruochen Cong ◽  
Xiangyang Zhu ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Early Stage ◽  
Infarct Volume ◽  
Intravenous Thrombolysis ◽  
Hounsfield Unit ◽  
Good Prognosis ◽  
Stroke Patients ◽  
Clinical Prognosis ◽  
Prognosis Group ◽  
Good Prognosis Group

Abstract Background: Intravenous thrombolysis (IVT) is a rapid and effective treatment in the early stage of ischemic stroke patients and the purpose of this work is to explore the significance of Hounsfield unit(HU) value in Alberta Stroke Program Early CT Score (ASPECTS) for predicting the clinical prognosis of stroke patients with middle cerebral artery occlusion (MCAO) treated by IVT. Methods: The 84 stroke patients with MCAO treated by IVT were divided into good prognosis group (48 cases) and poor prognosis group (36 cases). HU ratio and HU difference calculated from non-contrast computed tomography (NCCT) between groups were analyzed. Results: The HU ratio of good prognosis group was higher than that in poor prognosis group and the HU difference of good prognosis group was lower than that in poor prognosis group (P＜0.05). The HU ratio was negatively correlated with the infarct volume, and the HU difference was positively correlated with the infarct volume (P＜0.05). HU difference was an independent risk factor for prognosis of patients with MCAO treated by IVT. The area under the curve (AUC) of HU ratio and HU difference for prognosis was 0.743 and 0.833 respectively (P＜0.05). Conclusion: The HU value changes are related to the clinical prognosis of stroke patients with MCAO treated by IVT, HU value may be a prognostic indicator for stroke patients with MCAO treated by IVT.

scholarly journals Role of Diffusion Tensor Imaging Combined with Neuron-Specific Enolase and S100 calcium-binding protein B Detection in Predicting the Prognosis of Moderate and Severe Traumatic Brain Injury

2021 ◽  
Keyword(s):  
Poor Prognosis ◽  
Neuron Specific Enolase ◽  
Good Prognosis ◽  
S100b Protein ◽  
Control Group ◽  
The Poor ◽  
Severe Tbi ◽  
Prognosis Group ◽  
Good Prognosis Group

Background Traumatic brain injury (TBI) seriously affects the quality of life of patients. The present study evaluated the role of diffusion tensor imaging (DTI) combined with Neuron-Specific Enolase (NSE) and S100 calcium-binding protein B (S100B) protein in predicting the prognosis of moderate and severe TBI. Methods The TBI patients were divided into moderate TBI (TBIm) and severe TBI (TBIs) groups according to the Glasgow Coma Scale (GCS) after admission. The patients were then divided into good and poor prognosis groups according to the Glasgow Outcome Scale (GOS); moreover, their follow-ups were recorded at 3 and 6 months after injury. This study also included 65 healthy individuals with matched age and gender as the control group. The fractional anisotropy (FA) values of DTI, serum neuron-specific enolase (NSE), and S100B protein levels were detected in this study. The data were analyzed in SPSS software (version 22.0) to evaluate the role of DTI combined with NSE and S100B protein in predicting the prognosis in TBIm and TBIs. Results: After TBI, the FA values of DTI in the TBI group were lower than those in the control group (P<0.05); moreover, the serum NSE and S100B values in the TBI group were higher than those in the control group (P<0.05). In the TBIm patients, the FA values of the corpus callosum in the good prognosis group were higher than that in the poor prognosis group (P<0.05); however, there was no significant difference between the two groups regarding the FA values of the internal capsule and the cerebral peduncle (P>0.05). The serum levels of NSE and S100B in the good prognosis group were significantly lower than those in the poor prognosis group (P<0.05). In the TBIs patients, the FA value of all areas in the good prognosis group was significantly higher than that in the poor prognosis group (P<0.05). However, there was no significant difference between the two prognosis groups regarding the serum levels of NSE and S100B (P>0.05). Conclusion Although DTI combined with NSE and S100B protein can effectively predict the prognosis of patients with moderate and severe TBI in the early stages, various other measures have been used in the studies to predict the prognosis of TBI patients. Accordingly, comparison with other measures is essential in further studies.

Adaptation of chemotherapy to the decline tumor markers in patients with poor prognosis nonseminomatous germ cell tumors:Real-world French experience.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 385-385
Author(s):  
Marion Rolland ◽  
Sara Faouzi ◽  
Leonor Chaltiel ◽  
Clement Dumont ◽  
Lionnel Geoffrois ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Marker ◽  
Tumor Markers ◽  
Poor Prognosis ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
French Experience ◽  
Prognosis Group

385 Background: Personalized chemotherapy based on tumor marker decline is the new standard in poor prognosis germ-cell tumor in Europe since 2014 (GETUG 13, Lancet, Fizazi et al). The purpose of this study was to analyze the reproducibility of the princeps study in patients not selected in clinical routine between 2014 and 2018. Methods: Patients (pts) were eligible if they had at least one criteria of IGCCCG classification for poor prognosis group. They had to be treated according the study terms of GETUG 13 study and did not received prior treatment. They had to received 1 BEP (Bleomycin, Etoposide, Cisplatin). Tumor markers (HCG and AFP) were dosed between day 18 and 21. Then, they received 3 additional BEP if they had favorable tumor marker decline or intensive chemotherapy if they had unfavorable decline. Results: This retrospective study included 104 patients in 14 french centers treated between 2013 and 2018: 22,1 % (n = 23) in the favorable group (Fav), 77,9 % (n = 81) in the unfavorable group (Unfav). Thirty-two pts had PS ≥ 2. In Unfav, there were more pts with HCG > 50 000 UI/L (44,2 % vs 13 %, p = 0,0067), neutrophil-to-lymphocyt ratio was also higher (median 6,4 vs 4,5, p = 0,0199). At cycle 1, all pts received BEP in Fav and 87,5 % (n = 70) in Unfav. After chemotherapy and surgery, 65,2 % in Fav and 41,3 % in Unfav obtained complete response. At 30 months (median follow-up), Fav-OS was 80,5 % (IC95% 55,8 – 92,2) and Unfav-OS was 64,4 % (IC95% 52 – 74,4). At 30 months, rates were 69,6 % (IC95% 46,6 -84,2) and 63.5 % (IC95% 51,9 – 73) respectively. In GETUG 13 study, 3-years OS was 84 % in Fav and 73 % on Unfav; 3-years PFS was 70 % and 59 % respectively. Seven pts died because of toxicity in Unfav (No one in Fav). Neuropathy, anemia and thrombopenia were more frequent in Unfav. Salvage high-dose chemotherapy with stem-cell transplant was required in 4 (66,7 %) pts in Fav and 8 (36,4 %) pts in Unfav. Conclusions: This study showed a reproducibility of the princeps study in terms of PFS and OS. Toxicity seemed more important in real world. For the congress, results will be reported with 50 additional pts.

scholarly journals Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zuzana Cierna ◽  
Vera Miskovska ◽  
Jan Roska ◽  
Dana Jurkovicova ◽  
Lucia Borszekova Pulzova ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Lines ◽  
Poor Prognosis ◽  
Damage Identification ◽  
Excision Repair ◽  
Germ Cell Tumours ◽  
Expression Levels ◽  
Nucleotide Excision ◽  
Visceral Metastases ◽  
Prognosis Group

Abstract Background Germ cell tumours (GCTs) represent a highly curable malignity as they respond well to cisplatin (CDDP)-based chemotherapy. Nevertheless, a small proportion of GCT patients relapse or do not respond to therapy. As this might be caused by an increased capacity to repair CDDP-induced DNA damage, identification of DNA repair biomarkers predicting inadequate or aberrant response to CDDP, and thus poor prognosis for GCT patients, poses a challenge. The objective of this study is to examine the expression levels of the key nucleotide excision repair (NER) factors, XPA, ERCC1 and XPF, in GCT patients and cell lines. Methods Two hundred seven GCT patients’ specimens with sufficient follow-up clinical-pathological data and pairwise combinations of CDDP-resistant and -sensitive GCT cell lines were included. Immunohistochemistry was used to detect the ERCC1, XPF and XPA protein expression levels in GCT patients’ specimen and Western blot and qRT-PCR examined the protein and mRNA expression levels in GCT cell lines. Results GCT patients with low XPA expression had significantly better overall survival than patients with high expression (hazard ratio = 0.38, 95% confidence interval: 0.12–1.23, p = 0.0228). In addition, XPA expression was increased in the non-seminomatous histological subtype, IGCCCG poor prognosis group, increasing S stage, as well as the presence of lung, liver and non-pulmonary visceral metastases. Importantly, a correlation between inadequate or aberrant CDDP response and XPA expression found in GCT patients was also seen in GCT cell lines. Conclusions XPA expression is an additional independent prognostic biomarker for stratifying GCT patients, allowing for improvements in decision-making on treatment for those at high risk of refractoriness or relapse. In addition, it could represent a novel therapeutic target in GCTs.

Intensive Induction Chemotherapy With CBOP/BEP in Patients With Poor Prognosis Germ Cell Tumors

2003 ◽  
Vol 21 (5) ◽  
pp. 871-877 ◽  
Author(s):  
J.A. Christian ◽  
R.A. Huddart ◽  
A. Norman ◽  
M. Mason ◽  
S. Fossa ◽  
...  
Keyword(s):  
Germ Cell ◽  
Induction Chemotherapy ◽  
Poor Prognosis ◽  
Germ Cell Tumors ◽  
Phase Iii ◽  
Royal Marsden Hospital ◽  
Prognosis Group ◽  
Male Patients ◽  
Patients With Poor Prognosis

Purpose: Despite a high cure rate in patients with testicular cancer, there remain patients in the poor prognosis group who have a less favorable outcome. Intensive induction chemotherapy using a regimen consisting of carboplatin, bleomycin, vincristine, and cisplatin, followed by bleomycin, etoposide, and cisplatin (CBOP/BEP), developed at the Royal Marsden Hospital, is designed to overcome the rapid proliferation seen in germ cell tumors. This study assesses the outcome of patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) treated with CBOP/BEP. Patients and Methods: Patients with NSGCT from three centers, classified as poor prognosis according to International Germ Cell Classification Consensus Group criteria, were treated with CBOP/BEP regimen during the period from 1989 to 2000. Data on treatment toxicity, relapse-free survival (RFS), and overall survival (OS) were collected prospectively on a hospital database. Results: Fifty-four male patients with poor prognosis NSGCT were treated with CBOP/BEP. The RFS at 3 and 5 years for all patients was 83.2% (95% confidence interval [CI], 68.8% to 91.3%). After a median follow-up of 4 years, the OS of the 54 patients was 91.5% (95% CI, 78.6% to 96.8%) at 3 years and 87.6% (95% CI, 71.3% to 94.9%) at 5 years. Three-year OS in patients with a primary mediastinal germ cell tumor was 77.1% (95% CI, 34.5% to 93.9%) compared with 95.4% (95% CI, 82.8% to 98.8%) in patients with a testicular primary tumor (P = .24). Conclusion: The results reported here compare favorably with the historical results of alternative regimens used in the management of poor-prognosis NSGCT. We suggest a phase III trial to confirm our findings.

Brain tumor-initiating cells and cells of origin in glioblastoma

2011 ◽  
Vol 2 (4) ◽  
Author(s):  
Sameer Agnihotri ◽  
Diana Munoz ◽  
Gelareh Zadeh ◽  
Abhijit Guha
Keyword(s):  
Brain Tumour ◽  
Large Scale ◽  
Recent Literature ◽  
Cell Of Origin ◽  
Tumor Initiating Cells ◽  
Primary Brain Tumour ◽  
Cells Of Origin ◽  
Brain Tumor Initiating Cells ◽  
Candidate Regions

AbstractGlioblastoma Multiforme (GBM) is the most malignant and devastating primary brain tumour with a median survival of ∼12–16 months. Although recent large scale sequencing projects have shed considerable light into the complexity of the disease, there remains much to be elucidated in the hopes of generating effective therapeutic strategies. Although these studies investigate the mutations and expression of bulk tumour they have limits with respect to cell of origin and the concept of brain tumour initiating cells (BTIC). Current research has challenged the old paradigm of the stochastic model as recent evidence suggests that a subset of cancer cells within a tumor is responsible for tumor initiation, maintenance, and resistance to therapy. To gain a better understanding of the different compartment of cells that GBM comprise of require careful and elegant experiments. In addition to studying GBM, exploring the role of normal neural stem cells and progenitors cells is essential to partially explain whether these GBM BTIC behave similarly or differently then their non transformed counterparts. Here we discuss the recent literature between the two models, candidate regions of glioma genesis, candidate cells of origin for GBM, and possible therapeutic avenues to explore.

Extreme Regression: A Statistical Technique for Finding Good or Poor Prognostic Groups, Illustrated Using Myeloma Patient Data from Intergroup Trial S9321.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5202-5202 ◽  
Author(s):  
John J. Crowley ◽  
Jason McCoy ◽  
Michael LeBlanc ◽  
Bart Barlogie
Keyword(s):  
Median Survival ◽  
Survival Data ◽  
Poor Prognosis ◽  
Risk Group ◽  
Staging System ◽  
Statistical Technique ◽  
High Dose ◽  
Prognosis Group ◽  
Intergroup Trial ◽  
One Year

Abstract Extreme Regression (LeBlanc, Moon and Kooperberg, manuscript submitted) is a statistical technique for finding patient subsets with either very good or very poor prognosis. In contrast to Cox regression, which generates predictions based on linear combinations of variables, Extreme Regression results in groups based on intersections or unions of simple statements involving single covariates (eg sb2m &gt; 3.5 and albumin &lt; 3.5; sb2m &gt; 3.5 or LDH &gt; ULN). Thus, Extreme Regression is similar in spirit to tree-based regression methods, except that the goal is not to develop a complete staging system (like the new International Staging System, ISS, for myeloma, which was derived using tress-based methods) but rather to define subsets of a given size (eg 10%) with extreme prognosis. Here prognosis may be defined in terms of any type of outcome such as response, one-year mortality, overall survival, etc. To illustrate we use survival data from the Intergroup Trial S9321, which tested high dose therapy with melphalan and TBI versus a standard dose regimen of VBMCP (both after VAD induction) for newly diagnosed patients with multiple myeloma. We used as potential predictors serum beta-2 microglobulin (sb2m), LDH, albumin and creatinine as measured at baseline. There were 682 eligible patients with complete data on these four covariates. We asked the algorithm to identify roughly 10% of the patients representing a poor prognosis group, and then another 25% representing a good prognosis group. The results are shown in Figure 1, along with the intermediate group of all other patients. The poor risk group comprised 77 patients (11% of the total) and was defined by those patients with sb2m &gt; 9 and LDH &gt; ULN; or patients with creatinine &gt; 5; or patients with albumin &lt; 2. These patients had a median survival of 19 months, a one year survival of 66%, and a five year survival of 19%. The good risk group included 181 patients (27%) defined by LDH &lt;= 67% of ULN and creatinine &lt;= 2 and albumin &gt;= 3.5. This group had a median survival of 67 months, a one year survival of 96%, and a five year survival of 57%. Extreme regression appears to be a promising exploratory tool when the goal is the identification of simple, interpretable subsets of patients with extreme prognosis. Figure Figure

Comparing MicroRNA Expression In Aggressive and Indolent Non-Hodgkin Lymphomas Identifies a Prognostic Signature for Mantle Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 800-800
Author(s):  
Rashmi S. Goswami ◽  
Levi Waldron ◽  
Patricia P Reis ◽  
Yali Xuan ◽  
Wei Xu ◽  
...  
Keyword(s):  
B Cell ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Good Prognosis ◽  
Outcome Data ◽  
Training Set ◽  
Mantle Cell ◽  
Prognosis Group ◽  
Good Prognosis Group

Abstract Abstract 800 Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma (NHL) accounting for ~6% of all NHL. It is sensitive to combination chemotherapy, but remission durations are short without approaches such as stem cell transplantation (SCT). Most patients are incurable, but the clinical course is variable, with some patients succumbing quickly, while others survive >10 years. MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression by inhibiting mRNA translation. miRs are useful in the prognostic assessment of tumors, but work to date examining differences between MCL and normal lymphoid tissues, have only identified 2 miRs involved in MCL prognosis (Zhao JJ, Blood, 2010; Di Lisio L, Leukemia, 2010). We used a novel approach to identify a prognostic miR signature in MCL. We hypothesized that a miR signature defining aggressiveness can be obtained by comparing miR expression profiles of aggressive NHL with indolent NHL, and that this signature when applied to a set of MCL cases, may aid in MCL prognosis. Total RNA was extracted from 135 formalin-fixed paraffin-embedded samples obtained at primary diagnosis (Table 1). RNA from a training set of 19 indolent and 20 aggressive NHL cases was analyzed on a high-throughput quantitative real-time PCR (qRT-PCR) platform assessing the expression of 365 miRs and 3 endogenous controls (TaqMan Human MicroRNA Array v1.0: TLDA, ABI) using the DDCt method. A two-sample Wilcoxon Rank sum test corrected for false discovery rate was used to assess the significance of differential expression for each miR between aggressive and indolent NHL. The 14 most significantly differentially expressed miRs (p<0.001, FDR<0.02) were validated on an independent set of 25 indolent NHL and 19 aggressive NHL by qRT-PCR, and analyzed using the DDCt method. Univariate analysis using a one-sided t-test yielded 9 miRs that validated on the independent NHL set. Multivariable analysis demonstrated the ability of this 9 miR signature to distinguish between aggressive and indolent NHL (p<0.0001). Applying this signature to a set of 32 MCL patients with complete outcome data (Table 2) separated a poor prognosis group (median OS: 15 months, range: 4–40 months) from a good prognosis group (median OS: 88 months, range: 41–131 months) (Fig. 1). Among the 9 miRs were miR-29c, shown to have some prognostic value in MCL by Zhao et al., and miR-26a, shown to be important in MCL pathogenesis by Di Lisio et al. In light of the overlap with such recent studies, we believe the 9 miR prognostic signature we have identified may be of clinical utility. We are currently identifying mRNA targets for this miR signature and validating both the signature and the deregulated expression of these targets on a larger set of 200 MCL samples with known outcome data. Fig. 1. Psrincipal component analysis demonstrating separation of MCL cases into a good prognosis group in red (median OS: 88 months, range: 41–131 months) and a poor prognosis group in blue (median OS: 15 months, range: 4–40 months) based on expression of a 9 miR aggressiveness signature. Fig. 1. Psrincipal component analysis demonstrating separation of MCL cases into a good prognosis group in red (median OS: 88 months, range: 41–131 months) and a poor prognosis group in blue (median OS: 15 months, range: 4–40 months) based on expression of a 9 miR aggressiveness signature. Table 1. Sample breakdown Training set Number Aggressive cases Diffuse large B-cell lymphoma 5 Primary mediastinal B-cell lymphoma 5 Burkitt lymphoma 5 Atypical Burkitt 5 Indolent cases Small lymphocytic lymphoma/CLL 5 Extranodal marginal zone lymphoma 5 Follicular lymphoma Grade 1 3 Grade 2 3 Grade 3a 3 Validation set Aggressive cases Diffuse large B-cell lymphoma 7 Primary mediastinal B-cell lymphoma 5 Burkitt lymphoma 3 Atypical Burkitt 4 Indolent cases Small lymphocytic lymphoma/CLL 5 Extranodal marginal zone lymphoma 5 Follicular lymphoma Grade 1 5 Grade 2 5 Grade 3a 5 MCL cases Conventional 19 Blastoid/pleomorphic 11 Prolymphocytoid 1 Multiple lymphomatoid polyposis 1 Normal benign lymph nodes 20 TOTAL 135 Table 2. MCL clinical data Features Total % Gender Male 23 72 Female 9 28 ECOG 0 12 38 1 17 53 2-3 3 9 Stage 1 2 6 2 8 25 3 7 22 4 15 47 B symptoms 9 28 Extranodal sites 5 16 Lines of therapy 0 2 6 1 14 44 2 3 9 3 6 19 4 3 9 >4 4 13 Types of therapy Observation alone 2 6 Anthracycline-based 18 56 Rituximab 14 44 SCT 3 9 Bortezomib 3 9 Radiation 14 44 Median Range Age (yrs) 69 37–90 M-IPI score 6.6 5.3–8.7 Ki-67 (%) 25 7.5–90 Time to 1st treatment (months) 0.8 0.1–99.1 Overall survival (months) 34 4–131 Disclosures: Kuruvilla: Hoffman LaRoche: Honoraria, Research Funding; Celgene: Research Funding; Amgen: Honoraria; Otsuka: Honoraria; Genzyme: Honoraria.

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