CD317 Signature in Head and Neck Cancer Indicates Poor Prognosis

2018 ◽  
Vol 97 (7) ◽  
pp. 787-794 ◽  
Author(s):  
L.-L. Yang ◽  
L. Wu ◽  
G.-T. Yu ◽  
W.-F. Zhang ◽  
B. Liu ◽  
...  
Keyword(s):  
Head And Neck ◽  
Poor Prognosis ◽  
Histological Grade ◽  
Survival Curve ◽  
Tissue Microarrays ◽  
Immunocompetent Mouse ◽  
Tumor Associated Macrophage ◽  
Node Metastasis ◽  
Kaplan Meier ◽  
Meier Survival Curve

Targeted therapy using monoclonal antibodies (mAbs) has emerged as a widely used form of immunotherapy in head and neck squamous cell carcinoma (HNSCC). Membrane-associated glycoprotein CD317 has been preferentially overexpressed by multiple myeloma cells, and its humanized mAb has been previously used in clinical trials. However, overexpression of CD317 in HNSCC and its correlation with tumor immunity is still uncertain. Here, the immunoreactivity of CD317 was detected in human HNSCC tissue microarrays, which contained 43 oral mucosa samples, 48 dysplasia samples, and 165 primary HNSCC. We found that CD317 expression was up-regulated in HNSCC tumor cells, and the CD317 expression level was independent of the histological grade, tumor size, and lymph node metastasis. Moreover, Kaplan–Meier survival curve analysis showed that patients with high expression of CD317 had a poor prognosis compared with patients with low expression. Furthermore, CD317 overexpression in HNSCC was correlated with immune checkpoint molecules PD-L1, B7-H3, and B7-H4 and tumor-associated macrophage markers (CD68 and CD163). We also observed that CD317 was overexpressed in immunocompetent mouse HNSCC tissue compared with normal tissue. Taken together, our findings demonstrate that CD317 overexpression indicates poor prognosis and is correlated with immune-related components in this patient cohort. CD317 may serve as a potential target for effective immunotherapy of HNSCC.

scholarly journals A Prognostic Autophagy-Related Long Non-coding RNA (ARlncRNA) Signature in Acute Myeloid Leukemia (AML)

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunxia Zhao ◽  
Yulu Wang ◽  
Famei Tu ◽  
Shuai Zhao ◽  
Xiaoying Ye ◽  
...  
Keyword(s):  
Cox Regression ◽  
Survival Curve ◽  
Pearson Correlation ◽  
Enrichment Analysis ◽  
Risk Groups ◽  
Gene Set Enrichment Analysis ◽  
Kaplan Meier ◽  
Non Coding Rna ◽  
Novel Biomarkers ◽  
Meier Survival Curve

BackgroundSome studies have proven that autophagy and lncRNA play important roles in AML. Several autophagy related lncRNA signatures have been shown to affect the survival of patients in some other cancers. However, the role of autophagy related lncRNA in AML has not been explored yet. Hence, this study aims to find an autophagy related lncRNA signature that can affect survival for AML patients.MethodA Pearson correlation analysis, a Kaplan–Meier survival curve, a univariate cox regression, and a multivariate cox regression were performed to establish an autophagy related lncRNA signature. A univariate cox regression, a multivariate cox regression, a Kaplan–Meier survival curve, and a ROC curve were applied to confirm if the signature is an independent prognosis for AML patients. The relationship between the signature and the clinical features was explored by using a T test. Gene Set Enrichment Analysis (GSEA) was used to investigate the potential tumor related pathways.ResultsA four-autophagy related lncRNA (MIR133A1HG, AL359715.1, MIRLET7BHG, and AL356752.1) signature was established. The high risk score based on signature was related to the short survival time of AML patients. The signature was an independent factor for the prognosis for AML patients (HR = 1.684, 95% CI = 1.324–2.142, P < 0.001). The signature was correlated with age, leukocyte numbers, and FAB (M3 or non-M3). The P53, IL6/JAK/STAT3, TNF-α, INF-γ, and IL2/STAT5 pathways might contribute to the differences between the risk groups based on signature in AML.ConclusionThe four autophagy related lncRNAs and their signature might be novel biomarkers for predicting the survival of AML patients. Some biological pathways might be the potential mechanisms of the signature for the survival of AML patients.

scholarly journals Diagnostic and Prognostic Value of Presepsin in Patients with Non-Infectious Organ Failure, Sepsis, and Septic Shock: A Prospective Observational Study According to the Sepsis-3 Definitions

2021 ◽  
Author(s):  
Sukyo Lee ◽  
Juhyun Song ◽  
Dae Won Park ◽  
Hyeri Seok ◽  
Jae-hyung Cha ◽  
...  
Keyword(s):  
Septic Shock ◽  
Observational Study ◽  
Organ Failure ◽  
Prospective Observational Study ◽  
Survival Curve ◽  
Curve Analysis ◽  
Roc Curve Analysis ◽  
Kaplan Meier ◽  
Sepsis And Septic Shock ◽  
Meier Survival Curve

Abstract Background: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. Early diagnosis of sepsis is challenging due to unknown sources of infection, and mortality prediction is usually complex. We aimed to investigate the clinical value of presepsin for discriminating sepsis from non-infectious organ failure and predicting mortality among sepsis patients in the emergency department (ED).Methods: This prospective observational study included 420 patients divided into three groups according to the Sepsis-3 definitions: non-infectious organ failure (n=142), sepsis (n=141), and septic shock (n=137). Blood samples for biomarker measurement of presepsin, procalcitonin, and C-reactive protein were drawn in the ED and biomarker levels were compared between the groups. Optimal cut-off values for presepsin to discriminate between the three clinical diagnoses were evaluated using receiver operating characteristic (ROC) curve analysis. We also performed ROC curve analysis for each biomarker as a predictor of mortality. After excluding non-infectious organ failure, we extracted the optimal cut-off value of presepsin to predict mortality associated with sepsis and septic shock and performed Kaplan–Meier survival curve analysis according to the cut-off value.Results: Presepsin levels (median [IQR]) were significantly higher in sepsis than in non-infectious organ failure (792 [450–1273] vs. 286 [170–417], p <0.001) and significantly higher in septic shock than in sepsis (1287 [589–2365] vs. 792 [450–1273], p=0.002). The optimal cut-off value for presepsin to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (sensitivity, 70.1; specificity, 89.4; AUC, 0.877; p <0.001) and to discriminate between sepsis and septic shock was 1285 pg/mL (sensitivity, 50.4; specificity, 76.6; AUC, 0.618; p <0.001). The optimal cut-off value for presepsin for predicting 30-day mortality was 821 pg/mL (sensitivity, 68.9; specificity, 50.5; AUC, 0.605; p=0.005) in patients with sepsis and septic shock. Kaplan-Meier survival curve analysis showed that patients with higher presepsin levels (≥821 pg/mL) had significantly higher mortality than patients with lower presepsin levels (<821 pg/mL) (log-rank test; p=0.004). Conclusions: Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and septic shock from sepsis. Presepsin levels could help clinicians predict mortality in patients with sepsis and septic shock.

The Incidence Prognosis and Risk Factors of Cognitive Impairment in Maintenance Haemodialysis Patients

2018 ◽  
Vol 47 (1-3) ◽  
pp. 101-108 ◽  
Author(s):  
Renhua Lu ◽  
Chenqi Xu ◽  
Yan Li ◽  
Ling Yu ◽  
Xinghua Shao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Diastolic Pressure ◽  
Survival Curve ◽  
Maintenance Haemodialysis ◽  
Kaplan Meier ◽  
Education Status ◽  
Independent Risk Factors ◽  
Meier Survival Curve

Objective: To investigate the incidence and the prognosis of cognitive impairment (CI) and to find out the risk factors associated with the outcome in maintenance haemodialysis (MHD) patients. Methods: Enrolled the patients who met the criteria as below: MHD (≥3 months) patients before July 2014, ≥18 years old and could carry on the cognitive function test (Montreal Cognitive Assessment [MoCA]). All enrolled patients were divided into 2 groups: CI group (MoCA < 26) and non-CI group (MoCA ≥26). All patients were followed up for 36 months. The incidence, demography data, medical history, haemodialysis data, laboratory examination and prognosis of CI in haemodialysis patients were prospectively compared and analyzed. Multivariate logistic regression analysis was used to investigate the risk factors of CI. Kaplan-Meier survival curve was used for survival analysis. Results: In the present study, 219 patients were enrolled. The ratio of male to female was 1.46: 1. Age was 60.07 ± 12.44 and dialysis vintage was 100.79 ± 70.23 months. One hundred thirteen patients’ MoCA scores were lower than 26 were divided into CI group. Education status (OR 3.428), post-dialysis diastolic pressure (OR 2.234) and spKt/V (OR 1.982) were independent risk factors for CI in MHD patients. During the follow-up period, 15 patients died (13.2%) in the CI group and 5 died (4.72%) in the non-CI group (p < 0.05). The Kaplan-Meier survival curve analysis showed that the survival rate of patients with CI was lower than that of non-CI group in MHD patients during 3 years follow-up (p = 0.046). Conclusion: CI is one of the most common complications in MHD patients. The mortality is high in patients who had CI. Education status, post-dialysis diastolic pressure and spKt/V are independent risk factors for CI in MHD patients.

Abstract 14845: Masquerading Bundle Branch Block: An Electrocardiographic Marker of Poor Prognosis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Thiago G Schroder e Souza ◽  
Rômulo L Almeida ◽  
Gabriel P Targueta ◽  
Sandro P Felicioni ◽  
Virginia B Cerutti Pinto ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Survival Curve ◽  
Pacemaker Implantation ◽  
Epidemiological Data ◽  
Cardiac Conduction ◽  
Conduction Delay ◽  
S Wave ◽  
Bundle Branch Block ◽  
Kaplan Meier

Introduction: Masquerading bundle branch block (MBBB) is a rare cardiac conduction anomaly characterized in the Electrocardiogram (EKG) by Right Bundle Branch Block in the precordial leads and Left Bundle Branch Block in frontal leads. The available evidence indicates that it carries poor prognosis and that it is often underdiagnosed. We studied epidemiological peculiarities, electrocardiographic features and prognosis of this rare kind of ventricular conduction delay. Methods: In a review of over 600,000 EKGs from the database of Tele-Electrocardiography department of Dante Pazzanese Institute of Cardiology during the last seven years, we found twenty-five cases of MBBB. Diagnostic criteria were presence of QRS ≥ 0.12 s, dominant positive waves in V1, left axis deviation and absent or minimal S wave in DI and aVL. Epidemiological data was collected for each EKG and the follow-up of patient′s health status was assessed by telephone contact. Kaplan-Meier survival curves were based on the following endpoints: mortality, pacemaker implantation and the composite of both. Results: We identified twenty-five cases (21 males and 4 females) of MBBB. The average age was 69 (±14) years. Sinus rhythm was present in 17 patients (68%), atrial fibrillation in 7 (28%) and atrial flutter in one (4%). Average heart rate, PR interval, QRS length, QTc and QRS axis were, respectively: 70 (±17) bpm, 205 (±50) ms, 159 (±24) ms, 463 (±37) ms and -76° (±6) degrees. Follow-up data was successfully obtained from 15 patients: 4 (26.6%) had a pacemaker implanted, 7 (46.6%) died and 9 had combined endpoints (60%). According to the Kaplan-Meier survival curve, at 48 months, the estimated ratios of death, pacemaker implantation or combined endpoints were 41.4%, 38.9% and 80.2%, respectively. Conclusions: MBBB represents a high-risk condition and, although rare, this EKG pattern should be taken into consideration due to the poor prognosis associated with its presence.

DDRE-26. INHIBITION OF PRMT5 SENSITIZES GLIOBLASTOMA MODELS TO TRAMETINIB TREATMENT

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi79-vi80
Author(s):  
Yesh Banasavadi ◽  
Sriya Namagiri ◽  
yoshihiro Otani ◽  
Shilpa Thammegowda ◽  
Hannah Sur ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Survival Curve ◽  
Oral Gavage ◽  
Cycle Progression ◽  
Arginine Methyltransferase ◽  
Tumor Bearing ◽  
Nsg Mice ◽  
Kaplan Meier ◽  
Meier Survival Curve

Abstract With limited effective therapeutic strategies, the prognosis for glioblastoma (GBM) is very poor. Our previous study shows that the expression of Protein Arginine Methyltransferase 5 (PRMT5) is upregulated in GBM; its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. MEK inhibitors, including trametinib, are currently under investigation for GBM therapy. In this study, we tested whether inhibition of PRMT5 can enhance the anti-GBM efficacy of trametinib. Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot analysis were conducted. In vivo, PRMT5-intact and -depleted GBMNS were intracranially implanted in NSG mice and treated with trametinib by daily oral gavage, and tumor progression and mice survival rate were analyzed by MRI and Kaplan-Meier survival curve, respectively. Depletion of PRMT5 increased the cytotoxic effect of trametinib in GBMNS. Trametinib treatment increased the activity of ERBB3 and AKT; With PRMT5 knockdown, the activity of both AKT and ERBB3 decreased significantly. But, inhibition of ERBB3 alone failed to block the trametinib-induced AKT activity suggesting that even though PRMT5 regulates the activity of both ERBB3 and AKT, the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib treated GBMNS is because of AKT inhibition alone. In vivo, PRMT5-depletion extended the survival of the tumor-bearing mice that further increased in combination with trametinib treatment. Interestingly, trametinib treatment alone had no survival benefit.

scholarly journals In Vitro Fatigue Resistance of Teeth Restored With Bulk Fill versus Conventional Composite Resin

2016 ◽  
Vol 27 (4) ◽  
pp. 452-457 ◽  
Author(s):  
Gabrielle Branco Rauber ◽  
Jussara Karina Bernardon ◽  
Luiz Clovis Cardoso Vieira ◽  
Hamilton Pires Maia ◽  
Françoá Horn ◽  
...  
Keyword(s):  
Fatigue Resistance ◽  
Composite Resin ◽  
Survival Curve ◽  
Maximum Force ◽  
Lower Percentage ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Meier Survival Curve

Abstract The aim of this study was to compare the fatigue resistance of restored teeth with bulk fill composite resin, conventional composite resin with incremental insertion and unprepared sound teeth. Twenty-eight extracted maxillary premolars were selected and divided into 4 groups based on composite resin and insertion technique: control (C), conventional composite resin with incremental insertion (I) and bulk fill composite resin with three (BF3) or single increment (BF1). The restored specimens were submitted to fatigue resistance test with a 5 Hz frequency. An initial application of 5,000 sinusoidal load cycles with a minimum force of 50 N and a maximum force of 200 N was used. Next, were applied stages of 30,000 load cycles with the maximum force increasing gradually: 400, 600, 800, 1000, 1200 and 1400 N. The test was concluded when 185,000 load cycles were achieved or the specimen failed. The fatigue resistance data were recorded for comparison, using the Kaplan-Meier survival curve and analyzed by log-rank test at 0.05 significance. Fractures were classified based on the position of the failure - above or below the cementoenamel junction (CEJ). Statistical analysis of the Kaplan-Meier survival curve and log-rank test showed a significant difference between groups (p=0.001). The fracture analysis demonstrated that only 28.58% of failures were below the CEJ in group C, while for groups I, BF1 and BF3 they were 42.85%, 85.71% and 85.71%, respectively. Teeth restored with composite bulk fill in both techniques present similar fatigue resistance values compared with those restored with a conventional incremental insertion of composite, while the fatigue strength values of unprepared sound teeth were higher. Furthermore, unprepared sound teeth showed a lower percentage of fractures below the CEJ.

scholarly journals The Clinical and Pathological Significance of Nectin-2 and DDX3 Expression in Pancreatic Ductal Adenocarcinomas

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shan Liang ◽  
Zhulin Yang ◽  
Daiqiang Li ◽  
Xiongying Miao ◽  
Leping Yang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Poor Prognosis ◽  
Genetic Basis ◽  
Malignant Disease ◽  
Tnm Stage ◽  
Ductal Adenocarcinoma ◽  
Node Metastasis ◽  
Kaplan Meier ◽  
Poor Differentiation

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, but the genetic basis of PDAC is still unclear. In this study, Nectin-2 and DDX3 expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues were measured by immunohistochemical methods. Results showed that the percentage of positive Nectin-2 and DDX3 expression was significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P<0.01). The percentage of cases with positive Nectin-2 and DDX3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion and having TNM stage I/II disease than in patients with lymph node metastasis, invasion, and TNM stage III/IV disease (P<0.05orP<0.01). Positive DDX3 expression is associated with poor differentiation of PDAC. Kaplan-Meier survival analysis showed that positive Nectin-2 and DDX3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive Nectin-2 and DDX3 expression were independent poor prognosis factors in PDAC patients. In conclusion, positive Nectin-2 and DDX3 expression are associated with the progression and poor prognosis in PDAC patients.

scholarly journals Jaccoud’s arthropathy in SLE: findings from a Latin American multiethnic population

2019 ◽  
Vol 6 (1) ◽  
pp. e000343
Author(s):  
Rosana Quintana ◽  
Guillermo Pons-Estel ◽  
Karen Roberts ◽  
Monica Sacnún ◽  
Guillermo Berbotto ◽  
...  
Keyword(s):  
Disease Activity ◽  
Latin American ◽  
Survival Curve ◽  
Damage Index ◽  
Categorical Variables ◽  
Jaccoud’S Arthropathy ◽  
Kaplan Meier ◽  
Damage Accrual ◽  
Jaccoud's Arthropathy ◽  
Meier Survival Curve

ObjectiveTo compare the clinical, laboratory and outcome features of SLE patients with and without Jaccoud’s arthropathy (JA) from the Grupo Latino Americano De Estudio del Lupus (GLADEL) cohort.Methods1480 patients with SLE [(34 centres, 9 Latin American countries with a recent diagnosis (≤2 years)] constitute the GLADEL cohort. JA was defined as reducible deformity of the metacarpophalangeal axis, without radiographic erosions at any time. Within this cohort, a nested case–control study was carried out. Control was matched for age, gender and centre in a 1:3 proportion. The variables included were: sociodemographic, clinical and immunological features, disease activity, damage and mortality. Comparisons were performed with Wilcoxon and χ2 tests for continuous and categorical variables, respectively. ORs and 95% CIs and Kaplan-Meier survival curve were estimated.ResultsOf 1480 patients, 17 (1.1%) JA patients were identified; 16 (94.1%) of them were women, mean age: 31.0 years (SD 12.0). Five (29.4%) patients presented JA at SLE diagnosis and 12 (70.6%) after. The median follow-up time and all disease features were comparable in both groups except for a higher frequency of pneumonitis in the patients with JA [4 (23.5) vs 1 (2.0); p=0.012; (OR: 15.4; 95% CI 1.6 to 149.6)]. The SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage Index and the Kaplan-Meier survival curve were similar in both groups.ConclusionJA may tend to appear early in the course of SLE; it seems not to have an impact on disease activity, damage accrual or in survival.

Cytoplasmic Nucleophosmin (NPMc+) Mutations and FMS-Like Tyrosine Kinase 3 (Flt3) Internal Tandem Duplication (ITD) Mutations Cooperate to Cause Leukemia In a Mouse Model

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 145-145 ◽  
Author(s):  
Rachel E. Rau ◽  
Daniel Magoon ◽  
Emily McIntyre ◽  
Li Li ◽  
Sarah Greenblatt ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Median Survival ◽  
Myeloid Leukemia ◽  
Survival Curve ◽  
Erythroid Cells ◽  
Rt Pcr ◽  
Facs Analysis ◽  
Kaplan Meier ◽  
Meier Survival Curve

Abstract Abstract 145 NPMc+ mutations occur in up to 60% of adult and 20% of childhood acute myeloid leukemia (AML) with normal karyotype. Flt3 ITD mutations occur in 25% of adult and 15% of childhood AML. Flt3 ITD mutations occur twice as frequently in patients with NPMc+ mutations compared to those who lack a NPMc+ mutation. The presence of Flt3 ITD portends a poor prognosis. NPMc+ is associated with improved outcome, but only in the absence of a concomitant Flt3 ITD mutations. Given the high frequency with which these mutations occur together it is plausible that they cooperate to cause leukemia. However, this has yet to be demonstrated experimentally. To examine this, we crossed mice expressing a knock-in of an 18-bp ITD mutation in the juxtamembrane domain of the murine Flt3 gene (Flt3 wt/ITD) with transgenic mice expressing Flag-tagged type A NPMc+ mutation driven by the myeloid-specific human MRP8 promoter. Flt3wt/ITD mice develop a fatal myeloproliferative disorder (Li L, et al. Blood. 2008;111:3849-58) and NPMc+ transgenic mice develop a non-fatal myeloproliferation (Cheng K, et al. Blood. 2010;115-18), but neither develop leukemia, suggesting that cooperating events are required. Progeny were characterized by: 1) H&E staining of peripheral blood smears, bone marrow (BM) cytospins, and spleen sections; 2) FACS analysis of BM cells, splenocytes and thymocytes to determine the disease phenotype; 3) RT PCR to examine the expression of Flt3 ITD and NPMc+; and 4) immunofluorescence (IF) using an anti-Flag antibody to determine localization of the NPMc+ protein. Mice harboring both mutations develop acute leukemia with a median onset of 285 days (Figure 1). All the leukemic mice exhibit a moribund appearance, leukocytosis (mean WBC 69.3±32.7 vs 11.7±8.3K/μ L in wt/wt mice), splenomegaly (mean weight 0.63±0.3 vs 0.12±0.02g in wt/wt mice), anemia and thrombocytopenia. Four disease phenotypes based on FACS and histologic analysis have been observed (Figure 2). Thirty-three percent develop AML with infiltration of the BM and spleen with Mac1+/Gr1+ myeloblasts. Thiry-three percent develop T cell ALL with infiltration of BM, spleen, thymuses and other organs with abnormal CD3+/CD4+/CD8+ lymphoblasts. An additional 33% develop a mixed phenotype acute T/myeloid leukemia with both Mac1+/Gr1+ myeloblasts and CD3+/CD4+/CD8+ lymphoblasts. One mouse developed an undifferentiated acute leukemia with primitive blasts expressing no markers specific for either lymphoid or myeloid lineage. RT-PCR of bulk leukemia cells demonstrates expression of NPMc+ and Flt3 ITD. IF of BM cells from leukemic mice demonstrates cytoplasmic localization of the NPMc+ protein. In summary, we have utilized a mouse model to demonstrate that NPMc+ and Flt3 ITD mutations cooperate to cause leukemia. Many of the mice with both mutations develop myeloid leukemia with features similar to the human disease. There is also a striking incidence of T cell leukemia, which is particularly interesting as the NPMc+ mutation is driven by the myeloid-specific hMRP8 promotor. It is possible that there is aberrant expression of NPMc+ in lymphoid cells due to position effects of the transgene or the activation of an endogenous leukemogenic retrovirus. Other disease models using this promoter have documented similar phenomenon (Jaiswal, et al. PNAS. 2003;100:10002-7). There is a long latency of disease onset which may be due to a relatively low level of expression of NPMc+ or because additional genetic or epigenetic events are required. Perhaps the Flt3 ITD mutation causes proliferation and NPMc+ impairs DNA repair resulting in the accumulation of additional mutations that contribute to leukemogenesis. This mouse model provides the first in vivo model of NPMc+/Flt3 ITD+ leukemia. The model will allow for the further study of this disease entity, including the examination of involved pathways and the exploration for potential therapeutic targets. Kaplan-Meier Survival Curve. Mice with both NPMc+ and Flt3 ITD mutations have a median survival of 413 days. FACS analysis of leukemic mice BM cells and thymocytes. Mice with AML have cKit+/Mac1+/Gr1+ myelobasts. Mice with T cell ALL have infiltration of the BM, spleen (not shown) and thymus with CD3+/CD4+/CD8+ lymphoblasts. Mice with T/myeloid leukemia have both Mac1+/Gr1+ myeloblasts and CD3+/CD4+/CD8+ lymphoblasts. Leukemic mice have depletion of maturing Ter119+ erythroid cells. Figure 1 Kaplan-Meier Survival Curve. Mice with both NPMc+ and Flt3 ITD mutations have a median survival of 413 days. Figure 1. Kaplan-Meier Survival Curve. Mice with both NPMc+ and Flt3 ITD mutations have a median survival of 413 days. Figure 2 FACS analysis of leukemic mice BM cells and thymocytes. Mice with AML have cKit+/Mac1+/Gr1+ myelobasts. Mice with T cell ALL have infiltration of the BM, spleen (not shown) and thymus with CD3+/CD4+/CD8+ lymphoblasts. Mice with T/myeloid leukemia have both Mac1+/Gr1+ myeloblasts and CD3+/CD4+/CD8+ lymphoblasts. Leukemic mice have depletion of maturing Ter119+ erythroid cells. Figure 2. FACS analysis of leukemic mice BM cells and thymocytes. Mice with AML have cKit+/Mac1+/Gr1+ myelobasts. Mice with T cell ALL have infiltration of the BM, spleen (not shown) and thymus with CD3+/CD4+/CD8+ lymphoblasts. Mice with T/myeloid leukemia have both Mac1+/Gr1+ myeloblasts and CD3+/CD4+/CD8+ lymphoblasts. Leukemic mice have depletion of maturing Ter119+ erythroid cells. Disclosures: No relevant conflicts of interest to declare.

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