2020 |
Corboy G, Othman J, Lee L, Wei A, Ivey A, Blombery P, et al., 'Laboratory quality assessment of candidate gene panel testing for acute myeloid leukaemia: a joint ALLG / RCPAQAP initiative', Pathology, (2020)
© 2020 Royal College of Pathologists of Australasia Accurate classification of acute myeloid leukaemia (AML) has become increasingly reliant on molecular characterisation of this ... [more]
© 2020 Royal College of Pathologists of Australasia Accurate classification of acute myeloid leukaemia (AML) has become increasingly reliant on molecular characterisation of this blood cancer. Throughout Australia and New Zealand massively parallel sequencing (MPS) is being adopted by diagnostic laboratories for the routine evaluation of patients with AML. This technology enables the surveying of many genes simultaneously, with many technical advantages over single gene testing approaches. However, there are many variations in wet and dry lab MPS procedures, which raises the prospect of discordant results between laboratories. This study compared the results obtained from MPS testing of ten diagnostic AML bone marrow aspirate samples sent to eight participating laboratories across Australasia. A reassuringly high concordance of 94% was observed with regard to variant detection and characterisation of pathogenicity. The level of discordance observed, although low, demonstrates the need for ongoing assessment of concordance between diagnostic testing laboratories through quality assurance programs.
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2020 |
Berry NK, Scott RJ, Sutton R, Law T, Trahair TN, Dalla-Pozza L, et al., 'Enrichment of atypical hyperdiploidy and IKZF1 deletions detected by SNP-microarray in high-risk Australian AIEOP-BFM B-cell acute lymphoblastic leukaemia cohort', Cancer Genetics, 242 8-14 (2020) [C1]
© 2020 The Authors Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy with the majority of patients being classified as B-cell lineage (B-ALL). The sub-cl... [more]
© 2020 The Authors Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy with the majority of patients being classified as B-cell lineage (B-ALL). The sub-classification of B-ALL is based on genomic architecture. Recent studies have demonstrated the capability of SNP-microarrays to detect genomic changes in B-ALL which cannot be observed by conventional cytogenetic methods. In current clinical trials, B-ALL patients at high risk of relapse are mainly identified by adverse cancer genomics and/or poor response to early therapy. To test the hypothesis that inclusion of SNP-microarrays in frontline diagnostics could more efficiently and accurately identify adverse genomic factors than conventional techniques, we evaluated the Australian high-risk B-ALL cohort enrolled on AIEOP-BFM ALL 2009 study (n = 33). SNP-microarray analysis identified additional aberrations in 97% of patients (32/33) compared to conventional techniques. This changed the genomic risk category of 24% (8/33) of patients. Additionally, 27% (9/33) of patients exhibited a ¿hyperdiploid¿ genome, which is generally associated with a good genomic risk and favourable outcomes. An enrichment of IKZF1 deletions was observed with one third of the cohort affected. Our findings suggest the current classification system could be improved and highlights the need to use more sensitive techniques such as SNP-microarray for cytogenomic risk stratification in B-ALL.
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2020 |
Stevenson W, Bryant J, Watson R, Sanson-Fisher R, Oldmeadow C, Henskens F, et al., 'A multi-center randomized controlled trial to reduce unmet needs, depression, and anxiety among hematological cancer patients and their support persons', Journal of Psychosocial Oncology, 38 272-292 (2020) [C1]
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2020 |
Enjeti AK, de Malmanche T, Chapman K, Ziolkowski A, 'Genomic investigation of inherited thrombotic microangiopathy aHUS and TTP', International Journal of Laboratory Hematology, 42 33-40 (2020) [C1]
© 2020 John Wiley & Sons Ltd Thrombotic microangiopathies (TMA) are a heterogeneous group of red cell fragmentation syndromes characterized by a tendency for thrombosis and ... [more]
© 2020 John Wiley & Sons Ltd Thrombotic microangiopathies (TMA) are a heterogeneous group of red cell fragmentation syndromes characterized by a tendency for thrombosis and pathognomonic red cell fragments in peripheral blood, which results in thrombosis in the microvasculature due to endothelial damage. Genomic investigations into inherited TMAs are of diagnostic, prognostic and therapeutic value. Here, we present two cases that capture the importance of performing genomic testing in rare disorders. Treatment options for these conditions, such as plasma exchange and monoclonal antibodies against complement factors, are intensive and expensive health care interventions. The results of genomic investigation into rare TMAs can better inform the clinicians and their patients of prognosis and suitable personalized treatment options.
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2020 |
Bond DR, Lee HJ, Enjeti AK, 'Unravelling the epigenome of myelodysplastic syndrome: Diagnosis, prognosis, and response to therapy', Cancers, 12 1-25 (2020) [C1]
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2020 |
Bond DR, Uddipto K, Enjeti AK, Lee HJ, 'Single-cell epigenomics in cancer: charting a course to clinical impact', EPIGENOMICS, 12 (2020)
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2020 |
Murray HC, Enjeti AK, Kahl RGS, Flanagan HM, Sillar J, Skerrett-Byrne DA, et al., 'Quantitative phosphoproteomics uncovers synergy between DNA-PK and FLT3 inhibitors in acute myeloid leukaemia.', Leukemia, (2020)
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2020 |
Dun MD, Mannan A, Rigby CJ, Butler S, Toop HD, Beck D, et al., 'Shwachman Bodian Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and overexpressed in acute myeloid leukaemia', Leukemia, 34 3393-3397 (2020) [C1]
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2019 |
Arthur C, Jeffrey A, Yip E, Katsioulas V, Nalpantidis A, Kerridge I, et al., 'Prolonged administration of low-dose cytarabine and thioguanine in elderly patients with acute myeloid leukaemia (AML) achieves high complete remission rates and prolonged survival', LEUKEMIA & LYMPHOMA, 61 831-839 (2019)
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2019 |
Enjeti AK, Lincz LF, Seldon M, Isbister GK, 'Circulating microvesicles in snakebite patients with microangiopathy', RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, 3 121-125 (2019) [C1]
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2019 |
Joseph J, Rabbolini D, Enjeti AK, Favaloro E, Kopp M-C, McRae S, et al., 'Diagnosis and management of heparin-induced thrombocytopenia: a consensus statement from the Thrombosis and Haemostasis Society of Australia and New Zealand HIT Writing Group', MEDICAL JOURNAL OF AUSTRALIA, 210 509-515 (2019)
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2019 |
Chapman K, Scorgie FE, Ariyarajah A, Stephens E, Enjeti AK, Lincz LF, 'The effects of tetrahydrocurcumin compared to curcuminoids on human platelet aggregation and blood coagulation in vitro', Thrombosis Research, 179 28-30 (2019) [C1]
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2019 |
Sillar JR, Enjeti AK, 'Targeting apoptotic pathways in acute myeloid leukaemia', Cancers, 11 1-18 (2019) [C1]
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2019 |
Enjeti AK, Lincz LF, Seldon M, Isbister GK, 'Microangiopathy in snake bitesbubble trouble: Response to commentary', RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS, 3 298-299 (2019)
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2019 |
Berry NK, Scott RJ, Rowlings P, Enjeti AK, 'Clinical use of SNP-microarrays for the detection of genome-wide changes in haematological malignancies', Critical Reviews in Oncology/Hematology, 142 58-67 (2019) [C1]
© 2019 The Author(s) Single nucleotide polymorphism (SNP) microarrays are commonly used for the clinical investigation of constitutional genomic disorders; however, their adoption... [more]
© 2019 The Author(s) Single nucleotide polymorphism (SNP) microarrays are commonly used for the clinical investigation of constitutional genomic disorders; however, their adoption for investigating somatic changes is being recognised. With increasing importance being placed on defining the cancer genome, a shift in technology is imperative at a clinical level. Microarray platforms have the potential to become frontline testing, replacing or complementing standard investigations such as FISH or karyotype. This ¿molecular karyotype approach¿ exemplified by SNP-microarrays has distinct advantages in the investigation of several haematological malignancies. A growing body of literature, including guidelines, has shown support for the use of SNP-microarrays in the clinical laboratory to aid in a more accurate definition of the cancer genome. Understanding the benefits of this technology along with discussing the barriers to its implementation is necessary for the development and incorporation of SNP-microarrays in a clinical laboratory for the investigation of haematological malignancies.
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2019 |
Wei AH, Strickland SA, Hou J-Z, Fiedler W, Lin TL, Walter RB, et al., 'Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study', JOURNAL OF CLINICAL ONCOLOGY, 37 1277-+ (2019)
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2019 |
Simpson JD, Hopkins A, Amil A, Ross B, Enjeti AK, 'Transfusion-associated circulatory overload in ambulatory patients', Vox Sanguinis, 114 216-222 (2019) [C1]
© 2019 International Society of Blood Transfusion Background and Objectives: Transfusion-associated circulatory overload is a leading cause of transfusion-related adverse events. ... [more]
© 2019 International Society of Blood Transfusion Background and Objectives: Transfusion-associated circulatory overload is a leading cause of transfusion-related adverse events. The frequency and risks for transfusion-associated circulatory overload in ambulatory haematology patients are not known. Materials and Methods: A retrospective cohort analysis of ambulatory patients transfused in a tertiary haematology centre, using medical records and an electronic transfusion database, was undertaken between January and December 2014. Variables studied included age, gender, diagnosis, heart failure, kidney disease and details of transfusions. Transfusion-associated circulatory overload was defined according to proposed International Society of Blood Transfusion criteria. Patients with clinical evidence of hypervolaemia, not meeting the TACO definition and/or who were prescribed otherwise unscheduled diuretic agent, were collectively deemed to be at ¿risk of clinically significant hypervolaemia¿ (ROCSH). Results: In the study period, 93 ambulatory patients (male¿=¿49, female¿=¿44, mean age¿=¿75·89¿±¿11·37¿years) attended 715 transfusion encounters, totalling 1536 packed red cell units. No cases of TACO occurred whilst ¿ROCSH¿ events occurred in 57/715 (8%) of transfusion encounters. In a univariate model, age was significantly associated with ¿ROCSH¿, odds ratio¿=¿1·05 (P¿=¿0·017 95%, CI 1·01¿1·09) and no factors were significant on multivariate analysis. Conclusions: Transfusion-associated circulatory overload occurs infrequently haematology patients receiving ambulatory blood transfusions. To our knowledge, this is the first study to report on occurrence and risk factors for circulatory overload in ambulatory transfusions. This study provides vital baseline data for future prospective studies on this important aspect of haemovigilance.
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2018 |
Alkhatatbeh MJ, Enjeti AK, Baqar S, Ekinci EI, Liu D, Thorne RF, Lincz LF, 'Strategies for enumeration of circulating microvesicles on a conventional flow cytometer: Counting beads and scatter parameters.', Journal of Circulating Biomarkers, 7 1-10 (2018) [C1]
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2018 |
Staudt D, Murray HC, McLachlan T, Alvaro F, Enjeti AK, Verrills NM, Dun MD, 'Targeting Oncogenic Signaling in Mutant FLT3 Acute Myeloid Leukemia: The Path to Least Resistance', INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 19 (2018) [C1]
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2018 |
van der Pol E, Sturk A, van Leeuwen T, Nieuwland R, Coumans F, Mobarrez F, et al., 'Standardization of extracellular vesicle measurements by flow cytometry through vesicle diameter approximation', Journal of Thrombosis and Haemostasis, 16 1236-1245 (2018) [C1]
© 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis. Essentials Platele... [more]
© 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis. Essentials Platelet extracellular vesicles (EVs) concentrations measured by flow cytometers are incomparable. A model is applied to convert ambiguous scatter units to EV diameter in nanometer. Most included flow cytometers lack the sensitivity to detect EVs of 600 nm and smaller. The model outperforms polystyrene beads for comparability of platelet EV concentrations. Summary: Background Detection of extracellular vesicles (EVs) by flow cytometry has poor interlaboratory comparability, owing to differences in flow cytometer (FCM) sensitivity. Previous workshops distributed polystyrene beads to set a scatter-based diameter gate in order to improve the comparability of EV concentration measurements. However, polystyrene beads provide limited insights into the diameter of detected EVs. Objectives To evaluate gates based on the estimated diameter of EVs instead of beads. Methods A calibration bead mixture and platelet EV samples were distributed to 33 participants. Beads and a light scattering model were used to set EV diameter gates in order to measure the concentration of CD61¿phycoerythrin-positive platelet EVs. Results Of the 46 evaluated FCMs, 21 FCMs detected the 600¿1200-nm EV diameter gate. The 1200¿3000-nm EV diameter gate was detected by 31 FCMs, with a measured EV concentration interlaboratory variability of 81% as compared with 139% with the bead diameter gate. Part of the variation in both approaches is caused by precipitation in some of the provided platelet EV samples. Flow rate calibration proved essential because systems configured to 60 µL min-1 differed six-fold in measured flow rates between instruments. Conclusions EV diameter gates improve the interlaboratory variability as compared with previous approaches. Of the evaluated FCMs, 24% could not detect 400-nm polystyrene beads, and such instruments have limited utility for EV research. Finally, considerable differences were observed in sensitivity between optically similar instruments, indicating that maintenance and training affect the sensitivity.
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2018 |
Lapuz C, Enjeti AK, O'Brien PC, Capp AL, Holliday EG, Gupta SA, 'Outcomes and relapse patterns following chemotherapy in advanced Hodgkin lymphoma in the positron emission tomography era', BLOOD AND LYMPHATIC CANCER-TARGETS AND THERAPY, 8 13-20 (2018) [C1]
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2017 |
Ayyalil F, Irwin G, Ross B, Manolis M, Enjeti AK, 'Zeroing in on red blood cell unit expiry.', Transfusion, 57 2870-2877 (2017) [C1]
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2017 |
Lim MS, Ariyarajah A, Oldmeadow C, Hall A, Enjeti AK, 'A Systematic Review and Meta-analysis Comparing Anticoagulation versus No Anticoagulation and Shorter versus Longer duration of Anticoagulation for Treatment of Isolated Distal Deep Vein Thrombosis', Seminars in Thrombosis and Hemostasis, 43 836-848 (2017) [C1]
Isolated distal deep vein thrombosis (DVT) represents an important clinical problem but there is no consensus regarding its management. The aim of this review was to evaluate the ... [more]
Isolated distal deep vein thrombosis (DVT) represents an important clinical problem but there is no consensus regarding its management. The aim of this review was to evaluate the safety, efficacy, and shorter versus longer duration of anticoagulation in patients with isolated distal DVT. A systematic search was conducted using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systemic Reviews. Studies reporting rates of symptomatic pulmonary embolism (PE), recurrent DVT, proximal extension, and/or major bleeding were included. Fourteen studies (six randomized controlled trials, eight cohorts) involving 2,918 patients met the eligibility criteria (with a total of 13 meeting criteria for the meta-analysis). Compared with no anticoagulation, anticoagulation was associated with a significant reduction in proximal extension (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.13-0.67; p < 0.004), recurrent DVT (OR: 0.16; 95% CI: 0.04-0.65; p = 0.01), and the composite end-point of proximal extension/PE (OR: 0.34; 95% CI: 0.16-0.72; p = 0.005); however, no significant differences in PE (OR: 0.47; 95% CI: 0.17-1.34; p = 0.16) or major bleeding (OR: 1.49; 95% CI: 0.33-6.86; p = 0.60) were observed. Anticoagulation for a longer duration (=8 vs. =6 weeks) was associated with a significant reduction in proximal extension (OR: 0.23; 95% CI: 0.11-0.48; p < 0.001) but not for other outcomes.
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2017 |
Enjeti AK, Ariyarajah A, D'Crus A, Seldon M, Lincz LF, 'Circulating microvesicle number, function and small RNA content vary with age, gender, smoking status, lipid and hormone profiles', Thrombosis Research, 156 65-72 (2017) [C1]
© 2017 Background Characterization of circulating microvesicles (MV) in healthy subjects in relation to various biological factors is not well studied. Objectives We evaluated the... [more]
© 2017 Background Characterization of circulating microvesicles (MV) in healthy subjects in relation to various biological factors is not well studied. Objectives We evaluated the influence of age, gender, smoking status, lipid and hormone profiles on circulating MV in healthy subjects. Methods Platelet free plasma from 143 volunteer blood donors (males¿=¿80, females¿=¿63) was evaluated by standardized flow cytometry for MV expressing CD41 (platelet-derived), CD105 (endothelial-derived), CD235 (red cell-derived), TF (tissue factor) and phosphatidylserine (PS) MV. Procoagulant function was measured by the Xa based assay (XaCT) and endogenous thrombin potential (ETP) using thrombin generation assay. Results Those =¿29¿years and =¿60¿years had higher levels of MV subsets (CD41, CD235, TF and PS) compared to those aged 30¿59¿years. The median CD41, CD105, CD235, TF and PS expressing MV by flow cytometry were similar or lower in females, whilst procoagulant activity by the XaCT assay was higher (p¿=¿0.002). In smokers (n¿=¿21), certain MV subsets (CD41, TF and PS) and functional activity (ETP) was lower (p¿<¿0.05). Regression analysis showed that MV parameters of CD41, CD105, TF and ETP could be predicted independently by age, whilst smoking predicted for CD105, CD235, TF, PS and ETP. Certain MV parameters also correlated with BMI, lipid and hormone levels. The small RNA and miRNA levels did not differ by age group, smoking status or gender. Conclusions It is important to recognize that differences may arise depending on age, gender, BMI, lipid, hormone levels and smoking status in apparently healthy subjects when evaluating MV for pathogenic potential.
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2017 |
Berry NK, Dixon-McIver A, Scott RJ, Rowlings P, Enjeti AK, 'Detection of complex genomic signatures associated with risk in plasma cell disorders.', Cancer genetics, 218-219 1-9 (2017) [C1]
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2016 |
Lim MS, Lemmert K, Enjeti A, 'Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A rare entity', BMJ Case Reports, 2016 (2016)
Copyright 2016 BMJ Publishing Group. All rights reserved. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy in the elderly, w... [more]
Copyright 2016 BMJ Publishing Group. All rights reserved. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy in the elderly, with a high frequency of cutaneous and bone marrow involvement and poor prognosis. We report a case of BPDCN with classic presentation and discuss its treatment and the value of different investigation tools used in diagnosis and response assessment.
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2016 |
Enjeti AK, D'Crus A, Melville K, Verrills NM, Rowlings P, 'A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia', Anti-Cancer Drugs, 27 560-568 (2016) [C1]
© 2016 Wolters Kluwer Health, Inc. All rights reserved. Treatment of acute myeloid leukaemia (AML) is challenging and emerging treatment options include protein phosphatase 2A (PP... [more]
© 2016 Wolters Kluwer Health, Inc. All rights reserved. Treatment of acute myeloid leukaemia (AML) is challenging and emerging treatment options include protein phosphatase 2A (PP2A) activators. Fingolimod is a known PP2A activator that inhibits multiple signalling pathways and has been used extensively in patients with multiple sclerosis and other indications. The initial positive results of PP2A activators in vitro and mouse models of AML are promising; however, its safety for use in AML has not been assessed. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A literature review was carried out to assess safety before the commencement of Phase I trials of the PP2A activator Fingolimod in AML. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A systematic review of published literature in Medline, EMBASE and the Cochrane Library of critical reviews was carried out. International standards for the design and reporting of search strategies were followed. Search terms and medical subject headings used in trials involving PP2A activators as well as a specific search were performed for 'adverse events','serious adverse events', 'delays in treatment', ' side effects' and 'toxicity' for primary objectives. Database searches were limited to papers published in the last 12 years and available in English. The search yielded 677 articles. A total of 69 journal articles were identified as relevant and included 30 clinical trials, 24 review articles and 15 case reports. The most frequently reported adverse events were nausea, diarrhoea, fatigue, back pain, influenza viral infections, nasopharyngitis and bronchitis. Specific safety concerns include monitoring of the heart rate and conduction at commencement of treatment as cardiotoxicity has been reported. There is little evidence to suggest specific bone marrow toxicity. Lymophopenia is a desired effect in the management of multiple sclerosis, but may have implications in patients with acute leukaemia as it may potentially increase susceptibility to viral infections such as influenza. Fingolimod is a potential treatment option for AML with an acceptable risk to benefit ratio, given its lack of bone marrow toxicity and the relatively low rate of serious side effects. As most patients with AML are elderly, specific monitoring for cardiac toxicity as well as infection would be required.
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2016 |
Enjeti AK, Ariyarajah A, D'Crus A, Seldon M, Lincz LF, 'Correlative analysis of nanoparticle tracking, flow cytometric and functional measurements for circulating microvesicles in normal subjects', Thrombosis Research, 145 18-23 (2016) [C1]
© 2016 Introduction Circulating microvesicles (MV) can be analysed using a number of different techniques. The aim of this study was to evaluate the correlation between functional... [more]
© 2016 Introduction Circulating microvesicles (MV) can be analysed using a number of different techniques. The aim of this study was to evaluate the correlation between functional procoagulant based assays including thrombin generation, factor Xa activation test (XaCT), and phosphatidylserine factor Xa-activity by ELISA with optical MV enumeration by flow cytometry and nanoparticle tracking analysis. Methods Citrated blood samples were collected from 60 healthy volunteer blood donors after informed consent. Platelet free plasma was prepared using a standardized published protocol. MV subsets were enumerated by flow cytometry (BDFACS Canto) after staining with specific antibodies for platelets (CD41), endothelial cells (CD105), red cells (CD235) monocytes (CD14), tissue factor (CD142) and for phosphatidylserine expression by binding to annexin V. A standardized protocol using counting beads was employed. Nanotracking analysis was performed on both scatter and fluorescent settings after MV staining with quantum dot stain, Qdot 655. Procoagulant function was assessed by the XaCT assay on an automated coagulation analyser and by thrombin generation assay measuring endogenous thrombin potential (ETP), lagtime, peak (PEAK) and time to peak (ttPEAK) using a Calibrated Automated Thrombogram (CAT). The statistical analysis was carried out with Statistica 12 software using non-parametric tests (Spearman rank order correlations, with significance set at p¿<¿0.05). Results In normal healthy subjects, thrombin generation parameters correlated with levels of MV measured by flow cytometry. ETP, lagtime, ttPEAK and PEAK correlated with MV expressing phosphatidylserine (rs, Spearman rank order correlation was 0.29, 0.40, 0.31 and 0.34 respectively, p¿<¿0.05), and MV expressing tissue factor (rs was 0.29, 0.40, 0.31 and 0.34 respectively, p¿<¿0.05), whilst red cell derived MV correlated with lagtime, ttPEAK and PEAK (rs, was 0.35,0.30 and 0.3, respectively, p¿<¿0.05). Lagtime and ttPEAK negatively correlated with the clot based XaCT test (rs, was -¿0.34 and -¿0.30 respectively, p¿<¿0.05) and positively correlated with the ELISA MP-activity assay (rs¿=¿0.42 for both, p¿<¿0.05). In addition, endothelial MV levels weakly correlated with white cell counts (rs = 0.27, p¿<¿0.05). Conclusions Thrombin generation and flow cytometry for phosphatidylserine or tissue factor expressing MV correlate well as markers for procoagulant activity. A combination of optical or non-optical enumeration as well as functional methods may be required for a complete profiling of circulating MV.
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2016 |
Lim MS, Chapman K, Swanepoel P, Enjeti AK, 'Sensitivity of routine coagulation assays to direct oral anticoagulants: patient samples versus commercial drug-specific calibrators', Pathology, 48 712-719 (2016) [C1]
© 2016 Royal College of Pathologists of Australasia Most studies on the sensitivities of coagulation assays to direct oral anticoagulants (DOACs) are based on normal plasma spiked... [more]
© 2016 Royal College of Pathologists of Australasia Most studies on the sensitivities of coagulation assays to direct oral anticoagulants (DOACs) are based on normal plasma spiked with anticoagulant in the laboratory. Recent studies have shown that reagent sensitivity varies significantly depending on whether spiked or patient samples are used. The aim of this study was to compare the sensitivities of routine coagulation assays in patient samples and commercial drug specific calibrators using commonly used activated partial thromboplastin time (APTT) and prothrombin time (PT) reagents (i.e., Actin FS and Neoplastine CI Plus for APTT and PT, respectively) in Australian laboratories. Samples collected at Pathology North Hunter (PN-H) for dabigatran (n¿=¿39), rivaroxaban, (n¿=¿56) or apixaban levels (n¿=¿22) between February 2013 and November 2015 were analysed and compared to two different commercial drug specific calibrators from different manufacturers for each DOAC. Our results show that dabigatran (Hyphen and Technoclone) and rivaroxaban (Stago) calibrators tend to overestimate the APTT but are similar to patient samples for PT. A cut-off DOAC level of 50¿ng/mL based on results from patient samples within the laboratory can be used as the lower limit which will result in prolongation of APTT for dabigatran (sensitivity 96%, n¿=¿25) and PT for rivaroxaban (sensitivity 97%, n¿=¿29), respectively. Individual laboratories should be familiar with the sensitivity of their coagulation reagents to different DOACs including differences between patient samples versus different commercial drug specific calibrators.
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2016 |
Lim MS, Enjeti AK, 'Safety of anticoagulation in the treatment of venous thromboembolism in patients with haematological malignancies and thrombocytopenia: Report of 5 cases and literature review', CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 105 92-99 (2016) [C1]
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2016 |
Smith AM, Dun MD, Lee EM, Harrison C, Kahl R, Flanagan H, et al., 'Activation of protein phosphatase 2A in FLT3+ acute myeloid leukemia cells enhances the cytotoxicity of FLT3 tyrosine kinase inhibitors', Oncotarget, 7 47465-47478 (2016) [C1]
Constitutive activation of the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3), via co-expression of its ligand or by genetic mutation, is common in acute myeloid leuke... [more]
Constitutive activation of the receptor tyrosine kinase Fms-like tyrosine kinase 3 (FLT3), via co-expression of its ligand or by genetic mutation, is common in acute myeloid leukemia (AML). In this study we show that FLT3 activation inhibits the activity of the tumor suppressor, protein phosphatase 2A (PP2A). Using BaF3 cells transduced with wildtype or mutant FLT3, we show that FLT3-induced PP2A inhibition sensitizes cells to the pharmacological PP2A activators, FTY720 and AAL(S). FTY720 and AAL(S) induced cell death and inhibited colony formation of FLT3 activated cells. Furthermore, PP2A activators reduced the phosphorylation of ERK and AKT, downstream targets shared by both FLT3 and PP2A, in FLT3/ITD+ BaF3 and MV4-11 cell lines. PP2A activity was lower in primary human bone marrow derived AML blasts compared to normal bone marrow, with blasts from FLT3-ITD patients displaying lower PP2A activity than WT-FLT3 blasts. Reduced PP2A activity was associated with hyperphosphorylation of the PP2A catalytic subunit, and reduced expression of PP2A structural and regulatory subunits. AML patient blasts were also sensitive to cell death induced by FTY720 and AAL(S), but these compounds had minimal effect on normal CD34+ bone marrow derived monocytes. Finally, PP2A activating compounds displayed synergistic effects when used in combination with tyrosine kinase inhibitors in FLT3-ITD+ cells. A combination of Sorafenib and FTY720 was also synergistic in the presence of a protective stromal microenvironment. Thus combining a PP2A activating compound and a FLT3 inhibitor may be a novel therapeutic approach for treating AML.
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2015 |
Enjeti AK, Chapman K, Taylor PJ, Meldrum C, 'Congenital late onset thrombotic thrombocytopenic purpura: A diagnostic challenge', Pathology, 47 585-586 (2015) [C3]
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2015 |
Enjeti A, Granter N, Ashraf A, Fletcher L, Branford S, Rowlings P, Dooley S, 'A longitudinal evaluation of performance of automated BCR-ABL1 quantitation using cartridge-based detection system', Pathology, 47 570-574 (2015)
Copyright © 2015 Royal College of Pathologists of Australasia. All rights reserved. An automated cartridge-based detection system (GeneXpert; Cepheid) is being widely adopted in l... [more]
Copyright © 2015 Royal College of Pathologists of Australasia. All rights reserved. An automated cartridge-based detection system (GeneXpert; Cepheid) is being widely adopted in low throughput laboratories for monitoring BCR-ABL1 transcript in chronic myelogenous leukaemia. This Australian study evaluated the longitudinal performance specific characteristics of the automated system.The automated cartridge-based system was compared prospectively with the manual qRT-PCR-based reference method at SA Pathology, Adelaide, over a period of 2.5 years. A conversion factor determination was followed by four re-validations. Peripheral blood samples (n = 129) with international scale (IS) values within detectable range were selected for assessment. The mean bias, proportion of results within specified fold difference (2-, 3- and 5-fold), the concordance rate of major molecular remission (MMR) and concordance across a range of IS values on paired samples were evaluated.The initial conversion factor for the automated system was determined as 0.43. Except for the second re-validation, where a negative bias of 1.9-fold was detected, all other biases fell within desirable limits. A cartridge-specific conversion factor and efficiency value was introduced and the conversion factor was confirmed to be stable in subsequent re-validation cycles. Concordance with the reference method/laboratory at >0.1-=10 IS was 78.2% and at =0.001 was 80%, compared to 86.8% in the >0.01-=0.1 IS range. The overall and MMR concordance were 85.7% and 94% respectively, for samples that fell within ± 5-fold of the reference laboratory value over the entire period of study.Conversion factor and performance specific characteristics for the automated system were longitudinally stable in the clinically relevant range, following introduction by the manufacturer of lot specific efficiency values.
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2014 |
Berry NK, Bain NL, Enjeti AK, Rowlings P, 'Genomic profiling of plasma cell disorders in a clinical setting: integration of microarray and FISH, after CD138 selection of bone marrow', JOURNAL OF CLINICAL PATHOLOGY, 67 66-69 (2014) [C1]
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2013 |
Alkhatatbeh MJ, Enjeti AK, Acharya S, Thorne RF, Lincz LF, 'The origin of circulating CD36 in type 2 diabetes', NUTRITION & DIABETES, 3 (2013) [C1]
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2012 |
Lincz L, Scorgie FE, Enjeti A, Seldon M, 'Variable plasma levels of Factor V Leiden correlate with circulating platelet microparticles in carriers of Factor V Leiden', Thrombosis Research, 129 192-196 (2012) [C1]
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2011 |
Alkhatatbeh MJ, Mhaidat NM, Enjeti AK, Lincz L, Thorne RF, 'The putative diabetic plasma marker, soluble CD36, is non-cleaved, non-soluble and entirely associated with microparticles', Journal of Thrombosis and Haemostasis, 9 844-851 (2011) [C1]
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2011 |
Upanal NN, Enjeti A, 'Primary lymphoma of the uterus and cervix: Two case reports and review of the literature', Australian and New Zealand Journal of Obstetrics and Gynaecology, 51 559-562 (2011) [C3]
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2010 |
Enjeti A, Lincz L, Scorgie FE, Seldon MR, 'Circulating microparticles are elevated in carriers of Factor V Leiden', Thrombosis Research, 126 250-253 (2010) [C1]
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2008 |
Enjeti AK, Lincz L, Seldon MR, 'Bio-maleimide as a generic stain for detection and quantitation of microparticles', International Journal of Laboratory Hematology, 30 196-199 (2008) [C1]
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2008 |
Enjeti AK, Lincz L, Seldon MR, 'Microparticles in health and disease', Seminars in Thrombosis and Haemostasis, 34 683-692 (2008) [C1]
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2007 |
Enjeti AK, Lincz L, Seldon M, 'Detection and measurement of microparticles: An evolving research tool for vascular biology', Seminars in Thrombosis and Hemostasis, 33 771-779 (2007) [C1]
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2005 |
Enjeti AK, Walsh M, Seldon M, 'Spontaneous major bleeding in acquired factor X deficiency secondary to AL-amyloidosis', HAEMOPHILIA, 11 535-538 (2005)
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2005 |
Enjeti AK, Seldon M, Braye S, 'Bilateral breast lumps in a patient after sex mismatched allogeneic transplantation for aplastic anaemia', JOURNAL OF CLINICAL PATHOLOGY, 58 670-671 (2005)
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2004 |
Enjeti AK, Tien SL, Sivaswaren CR, 'Cytogenetic abnormalities in de novo acute myeloid leukemia in adults: Relation to morphology, age, sex and ethnicity - A single center study from Singapore', Hematology Journal, 5 419-425 (2004)
Background: Cytogenetic analysis performed at diagnosis is considered to be the most valuable prognostic factor in acute myeloid leukemia (AML). Large systematic studies of cytoge... [more]
Background: Cytogenetic analysis performed at diagnosis is considered to be the most valuable prognostic factor in acute myeloid leukemia (AML). Large systematic studies of cytogenetic abnormalities in AML patients from Southeast Asia are not available. The karyotypic patterns in AML patients from a single center in Singapore were studied and compared with reports from other regions of the world to identify possible geographic heterogeneity. Methods: Analysis was performed on 501 consecutive de novo AML patients diagnosed according to the FAB criteria in the Singapore General Hospital. The cytogenetic findings were analyzed for possible associations between karyotypic pattern and the age, gender, ethnicity as well as morphological (FAB) subtypes. Results: A total of 454 patients were studied of which 275(61%) had abnormal cytogenetics (median age 48 years). The t(15;17) and trisomy 8 were the most frequent karyotypic abnormalities - seen in 52(11%) and 33(7.3%) cases, respectively. Inv(16) and t(16;16) were uncommon, seen only in five (1.1%) cases. The abnormalities del 5/5q and del 7/7q were seen in 30(6.6%) and 32(7%) of the cases. Complex karyotypes were seen in 78(17%) of the cases. Recurrent cytogenetic abnormalities correlated with the FAB subtypes. In all, 21 novel cytogenetic abnormalities were observed. Conclusions: Certain differences such as the age at presentation and frequency of recurrent balanced translocations were noted in comparison to previous reports. These point to the need for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML. © 2004 The European Hematology Association All rights reserved.
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