Dataset Information

Transcriptomic and proteomic analysis of mouse radiation-induced acute myeloid leukaemia (AML).

ABSTRACT: A combined transcriptome and proteome analysis of mouse radiation-induced AMLs using two primary AMLs, cell lines from these primaries, another cell line and its in vivo passage is reported. Compared to haematopoietic progenitor and stem cells (HPSC), over 5000 transcriptome alterations were identified, 2600 present in all materials. 55 and 3 alterations were detected in the proteomes of the cell lines and primary/in vivo passage material respectively, with one common to all materials. In cell lines, approximately 50% of the transcriptome changes are related to adaptation to cell culture, and in the proteome this proportion was higher. An AML 'signature' of 17 genes/proteins commonly deregulated in primary AMLs and cell lines compared to HPSCs was identified and validated using human AML transcriptome data. This also distinguishes primary AMLs from cell lines and includes proteins such as Coronin 1, pontin/RUVBL1 and Myeloperoxidase commonly implicated in human AML. C-Myc was identified as having a key role in radiation leukaemogenesis. These data identify novel candidates relevant to mouse radiation AML pathogenesis, and confirm that pathways of leukaemogenesis in the mouse and human share substantial commonality.

SUBMITTER: Badie C

PROVIDER: S-EPMC5130020 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Transcriptomic and proteomic analysis of mouse radiation-induced acute myeloid leukaemia (AML).

Badie Christophe C Blachowicz Agnieszka A Barjaktarovic Zarko Z Finnon Rosemary R Michaux Arlette A Sarioglu Hakan H Brown Natalie N Manning Grainne G Benotmane M Abderrafi MA Tapio Soile S Polanska Joanna J Bouffler Simon D SD

Oncotarget 20160601 26

A combined transcriptome and proteome analysis of mouse radiation-induced AMLs using two primary AMLs, cell lines from these primaries, another cell line and its in vivo passage is reported. Compared to haematopoietic progenitor and stem cells (HPSC), over 5000 transcriptome alterations were identified, 2600 present in all materials. 55 and 3 alterations were detected in the proteomes of the cell lines and primary/in vivo passage material respectively, with one common to all materials. In cell l ...[more]

PMID: 27250028

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Project description:BackgroundsAn increasing incidence of Acute Myeloid Leukaemia (AML) has been reported in several Western countries. However, the epidemiology of AML in Asia is very limited. According to the National Comprehensive Cancer Network (NCCN) guideline of AML, a range of conventional therapy options is available to AML patients. Nevertheless, different treatment strategies may result in diverse healthcare utilization and costs. Understanding the treatment patterns, healthcare utilization and costs of AML would thus be essential for clinicians and policymakers to optimize the treatment strategies of AML.ObjectivesThe objective of this study was to investigate the incidence, treatment patterns, healthcare utilization and costs of AML in Taiwan using a nationwide population database.MethodsWe retrospectively identified AML patients diagnosed from 2006 to 2015 from the Taiwan Cancer Registry Database (TCRD) and estimated the epidemiology of AML in Taiwan. The TCRD was linked to National Health Insurance Research Database (NHIRD) to collect the treatment patterns and health care utilization. Patients diagnosed with AML from 2011 to 2015 were further identified to analyze treatment patterns, healthcare utilization and costs.ResultsThe crude annual incidence of AML increased from 2.78 to 3.21 cases per 100,000 individuals from 2006 to 2015. However, the age-standardized rate (ASRs) of AML slightly declined from 2.47 to 2.41 cases per 100,000 individuals in the same period. Among 2,179 AML patients who received induction therapy (median age: 56 years), most of them (n = 1744; 80.04%) received standard-dose cytarabine (SDAC) regimen. The remaining 162 patients received high dose cytarabine (HDAC) and 273 patients received non-standard dose cytarabine (N-SDAC) regimen as the induction therapy. The median medical costs in our study for patients treated with chemotherapy alone was $42,271 for HDAC, $36,199 for SDAC and $36,250 for N-SDAC. For those who received hematopoietic stem cell transplantation (HSCT) after induction therapy, their median medical costs were $78,876 for HDAC, $78,593 for SDAC and $79,776 for N-SDAC.ConclusionsThis study is the first population-based study conducted in Asia to provide updated and comprehensive information on epidemiology, treatment patterns and healthcare resource utilization and costs of AML.

Project description:BackgroundBased on the results from the ALFA-0701 study, gemtuzumab ozogamicin (GO) has been approved by the European Medicine Agency and by the Italian Drug Agency for the first line treatment of de novo acute-myeloid leukemia (AML). In this analysis, we assessed the cost-effectiveness of GO in combination with daunorubicin and cytarabine (DA), vs DA alone, adopting the perspective of the Italian National Health Service.MethodsFor this analysis, a cohort state transition model was developed. The model was designed to capture health states and events that occur throughout the entire disease course and that impact costs and outcomes. The ALFA-0701 study was the main source of clinical data for this analysis. In the model, patients had the same baseline characteristics and experienced the same clinical improvements as in the ALFA-0701 study. Economic data (resource consumption and unit costs) were adapted to reflect expenditure for the Italian National Health Service. Utilities per health state and disutilities due to adverse events were based on the literature and on the general population for those functionally cured. A lifetime horizon was adopted, with both costs and outcome being discounted of 3.0%, annually. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of results.ResultsIn the base case (lifetime horizon; primary source of data: study ALFA-0701; perspective: Italian National Health Service; discount rate on costs and outcomes: 3.0%), GO + DA was more effective DA both in terms of life-year (LY) survival (6.42 LY vs 5.75 LY, respectively) and quality-of-life adjusted survival (4.69 QALY vs 4.19 QALY, respectively). The overall costs were almost similar in the two groups (slightly lower with GO + DA than with DA; €162,424 and €162,708, respectively). The use of GO increased the costs of drug therapy but saved costs of relapse and costs associated with transplantation (HSCT).ConclusionsIf results of the ALFA-0701 study are applied to the Italian healthcare environment, then gemtuzumab ozogamicin, in combination with daunorubicin and cytarabine, would clinical outcomes and reduce lifetime costs, compared with daunorubicin and cytarabine alone for the first line treatment of de novo AML.Trial registrationNot applicable.

Dataset Information

Transcriptomic and proteomic analysis of mouse radiation-induced acute myeloid leukaemia (AML).

Publications

Transcriptomic and proteomic analysis of mouse radiation-induced acute myeloid leukaemia (AML).

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