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  1. Fulltext Molecular mechanisms underlying the clinical efficacy of panobinostat involve Stochasticity of epigenetic signaling, sensitization to anticancer drugs, and induction of cellular cell death related to cellular stresses
    El Omari N, Bakrim S, Khalid A, Abdalla AN, Almalki WH, Lee LH, et al.
    Biomed Pharmacother, 2023 Aug;164:114886.
    PMID: 37224752 DOI: 10.1016/j.biopha.2023.114886
    Panobinostat, also known as Farydak®, LBH589, PNB, or panobinostat lactate, is a hydroxamic acid that has been approved by the Food and Drug Administration (FDA) for its anti-cancer properties. This orally bioavailable drug is classified as a non-selective histone deacetylase inhibitor (pan-HDACi) that inhibits class I, II, and IV HDACs at nanomolar levels due to its significant histone modifications and epigenetic mechanisms. A mismatch between histone acetyltransferases (HATs) and HDACs can negatively affect the regulation of the genes concerned, which in turn can contribute to tumorigenesis. Indeed, panobinostat inhibits HDACs, potentially leading to acetylated histone accumulation, re-establishing normal gene expression in cancer cells, and helping to drive multiple signaling pathways. These pathways include induction of histone acetylation and cytotoxicity for the majority of tested cancer cell lines, increased levels of p21 cell cycle proteins, enhanced amounts of pro-apoptotic factors (such as caspase-3/7 activity and cleaved poly (ADP-ribose) polymerase (PARP)) associated with decreased levels of anti-apoptotic factors [B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra-large (Bcl-XL)], as well as regulation of immune response [upregulated programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression] and other events. The therapeutic outcome of panobinostat is therefore mediated by sub-pathways involving proteasome and/or aggresome degradation, endoplasmic reticulum, cell cycle arrest, promotion of extrinsic and intrinsic processes of apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this investigation, we aimed to pinpoint the precise molecular mechanism underlying panobinostat's HDAC inhibitory effect. A more thorough understanding of these mechanisms will greatly advance our knowledge of cancer cell aberrations and, as a result, provide an opportunity for the discovery of significant new therapeutic perspectives through cancer therapeutics.
    Matched MeSH terms: United States
  2. Insertion of single-chain variable fragment (scFv) peptide linker improves surface display of influenza hemagglutinin (HA1) on non-recombinant Lactococcus lactis
    Jee PF, Chen FS, Shu MH, Wong WF, Abdul Rahim R, AbuBakar S, et al.
    Biotechnol Prog, 2017 Jan;33(1):154-162.
    PMID: 27802566 DOI: 10.1002/btpr.2400
    Heterologous protein displayed on the surface of Lactococcus lactis using the binding domain of N-acetylmuramidase (AcmA) has a potential application in vaccine delivery. In this study, we developed a non-recombinant L. lactis surface displaying the influenza A (H1N1) 2009 hemagglutinin (HA1). Three recombinant proteins, HA1/L/AcmA, HA1/AcmA, and HA1 were overexpressed in Escherichia coli, and purified. In the binding study using flow cytometry, the HA1/L/AcmA, which contained the single-chain variable fragment (scFv) peptide linker showed significantly higher percentage of binding counts and mean fluorescence binding intensity (MFI) (51.7 ± 1.4% and 3,594.0 ± 675.9, respectively) in comparison to the HA1/AcmA without the scFv peptide linker (41.1 ± 1.5% and 1,652.0 ± 34.1, respectively). Higher amount of HA1/L/AcmA (∼2.9 × 10(4) molecules per cell) was displayed on L. lactis when compared to HA1/AcmA (∼1.1 × 10(4) molecules per cell) in the immunoblotting analysis. The HA1/L/AcmA completely agglutinated RBCs at comparable amount of protein to that of HA1/AcmA and HA1. Computational modeling of protein structures suggested that scFv peptide linker in HA1/L/AcmA kept the HA1 and the AcmA domain separated at a much longer distance in comparison to HA1/AcmA. These findings suggest that insertion of the scFv peptide linker between HA1 and AcmA improved binding of recombinant proteins to L. lactis. Hence, insertion of scFv peptide linker can be further investigated as a potential approach for improvement of heterologous proteins displayed on the surface of L. lactis using the AcmA binding domain. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:154-162, 2017.
    Matched MeSH terms: United States
  3. Reflections on the maternal mortality millennium goal
    Lawson GW, Keirse MJ
    Birth, 2013 Jun;40(2):96-102.
    PMID: 24635463 DOI: 10.1111/birt.12041
    Nearly every 2 minutes, somewhere in the world, a woman dies because of complications of pregnancy and childbirth. Every such death is an overwhelming catastrophe for everyone confronted with it. Most deaths occur in developing countries, especially in Africa and southern Asia, but a significant number also occur in the developed world.
    Matched MeSH terms: United States
  4. Cross-cultural perspectives on birth practices
    Laderman C
    Birth, 1988 Jun;15(2):86-7.
    PMID: 3390277
    Matched MeSH terms: United States
  5. The Body Acceptance by Others Scale-2 (BAOS-2): Psychometric properties of a Bahasa Malaysia (Malay) translation and an assessment of invariance across Malaysia, the United Kingdom, and the United States
    Swami V, Todd J, Barron D, Wong KY, Zahari HS, Tylka TL
    Body Image, 2021 Sep;38:346-357.
    PMID: 34091281 DOI: 10.1016/j.bodyim.2021.05.009
    The Body Acceptance by Others Scale-2 (BAOS-2) is a 13-item instrument measuring generalised perceptions of body acceptance by others. Here, we first demonstrate that a Bahasa Malaysia (Malay) translation of the BAOS-2 is psychometrically valid in a sample of 1,049 Malaysian adults (Study 1). Using exploratory and confirmatory factor analysis, we extracted a unidimensional model of BAOS-2 scores that retained all 13 items. BAOS-2 scores had adequate internal consistency and indices of validity (convergent, construct, concurrent, and incremental), and were scalar invariant across gender and ethnicity (Malaysian Malays vs. Chinese). Next, we assessed invariance of BAOS-2 scores across samples from Malaysia, the United Kingdom, and the United States (total N = 2,575; Study 2). Multi-group confirmatory factor analysis showed that partial scalar invariance was achieved. Participants in the interdependent cultural context of Malaysia had significantly higher scores - with small effect sizes - than their counterparts in the independent contexts of the United Kingdom and United States. In addition, women had significantly higher scores than men, but the effect size was negligible. The present study indicates that the Malay BAOS-2 is a psychometrically valid instrument and presents the first comparison of BAOS-2 scores across interdependent and independent contexts.
    Matched MeSH terms: United States
  6. Measurement invariance of the Broad Conceptualization of Beauty Scale (BCBS) across Black, Hispanic, and White women in the United States
    Modica CA, DiLillo V, Swami V
    Body Image, 2023 Mar;44:69-77.
    PMID: 36502544 DOI: 10.1016/j.bodyim.2022.11.008
    The Broad Conceptualization of Beauty Scale (BCBS) assesses the degree to which women perceive diverse appearances and internal qualities as being beautiful. Although the instrument is increasingly used in diverse national and linguistic contexts, no previous study has examined measurement invariance of the BCBS across racial groups. To rectify this, we asked 395 Black, 406 Hispanic, and 423 White women from the United States to complete the BCBS. Confirmatory factor analysis indicated that a unidimensional model of BCBS scores had poor fit to the data in the total sample, but freely estimating error covariances between six pairs of items resulted in adequate fit. Additionally, full configural and scalar invariance was supported, but metric invariance was not, with further testing indicating that the item loading for one item differed across groups. Comparison of latent means indicated that all between-groups comparisons in BCBS scores were non-significant. However, medium-sized group differences in BCBS scores emerged once group differences in key demographics were controlled for. Overall, these results suggest that the BCBS largely achieves measurement invariance across Black, Hispanic, and White women in the United States, suggestive of similarity in how the construct of broad conceptualisation of beauty is understood and experienced.
    Matched MeSH terms: United States
  7. Fulltext Mitigation measures during elections and it’s impacts on COVID-19 Pandemic: Sabah State (Malaysia), New Zealand and the United States
    Syaza Zainudin, Mohd Amiruddin Mohd Kassim, Nor Nadia Mohamad Ridza
    Borneo Epidemiology Journal, 2020;1(2):145-156.
    MyJurnal
    Background and Objective: Countries all over the world respect the election process as one of the fundamental steps in forming a government. However, the exponential spread of COVID-19 has been deeply alarming, with a high number of positive cases and total deaths, forcing World Health Organization to declare it as a pandemic on 11thMarch 2020. During these unprecedented events, governments have had a tough decision to balance between the constitutional obligation to hold an election and the safety of the people. As such, electoral commissions have implemented numerous approaches to allow election to proceed in a safe and controlled setting during the pandemic.
    Methods: The preventative measures and standard operating procedures in the Sabah state of Malaysia, NewZealand and the United States elections are discussed, as well as COVID-19 post-election situation in respective countries. Innovative approaches and election flexibilities shall be considered to allow voting in the safest way possible, following the new normal.
    Discussion:Nevertheless, countries need to evaluate its strength of public health response when deciding to hold elections due to potential devastating outbreaks following elections despite measures taken.
    Conclusion: The election is a fundamental process in a democracy. Countries are required to be flexible and innovative in their approach to hold a safe election. Nevertheless, it may be prudent for countries with fewer resources and poor pandemic control to postpone election as a rise in cases will be catastrophic, putting many lives at risk.
    Matched MeSH terms: United States
  8. Fulltext Recent Advances in Breast Cancer Diagnosis Entering an Era of Precision Medicine
    Lim, Christopher, Mra, Aung, Chin, Suliong, Venkata Rao, Challa, Aung, Tun, Sieman, Jony, et al.
    Borneo Journal of Medical Sciences, 2019;13(1):3-9.
    MyJurnal
    This article will cover some of the most recent advances in the diagnosis of the world’s most common cancer in women, namely, breast cancer as we enter the era of precision medicine. The authors will discuss the differences between East and West pertaining to the incidence and mortality rates, the types of breast cancer and the revised staging criteria of breast cancer according to the American Joint Committee on Cancer (AJCC) Staging Manual, 8th edition. In addition, the advances of newer imaging modalities are presented and compared with traditional ultrasonography and mammography
    Matched MeSH terms: United States
  9. Fulltext Supraventricular Tachycardia: An Unusual Side Effects of Cefuroxime
    Yeap, Boon Tat, Yeoh, Boon Seng, Rajesh Kumar Muniandy
    Borneo Journal of Medical Sciences, 2019;13(2):35-38.
    MyJurnal
    Anaphylactic reaction towards antibiotics is common during anaesthesia. It may present as bronchospasm, hypotension, desaturation, or urticarial. However it is uncommon for anaphylaxis reaction to present only as supraventricular tachycardia (SVT). This is a rare interesting case report on a 23-year-old healthy man whose anaesthetic categorization is American Society of Anaesthesiologist (ASA) 1, developed supraventricular tachycardia (SVT) towards intravenous cefuroxime, peri operatively. His condition resolved with carotid sinus massage. No pharmacological interventions were used. His skin prick intradermal tests showed allergies towards cefuroxime, cefazoline and cefoperazone. The patient subsequently underwent.
    Matched MeSH terms: United States
  10. Fulltext Prevalence and Risk Factors of Low Birth Weight Infants in Hospital Wanita dan Kanak-kanak Sabah from 2014 – 2017
    Tan, Bee Hwai
    Borneo Journal of Medical Sciences, 2018;12(101):37-38.
    MyJurnal
    There is a strong need to reduce costs of hospital and advocating health economics in countries like the United States of America. The rising cost of healthcare globally especially in the United States of America has interestingly outraged the temper of many citizens about the Obamacare and Trumpcare. The issue about high cost in healthcare is the failure for people globally to recognize that healthcare facility is a 24-hour round-the-clock service. It therefore involves doubling of the utility bills, tripling the manpower due to shifts and rest, wear-and-tear of basic electrical devices is short-lived, breakdown period of huge machine is consistently due to overloaded usages in the government hospitals and poor knowledge of the maintenance programme. Low birth weights (LBW) is a public health concern because it has a well-known predisposition to increased risk for perinatal infections, respiratory distress and ultimately mortality. There is also a higher risk of poor health outcomes throughout the life course of the LBW newborns that includes Type 2 diabetes, high blood pressure, neurodevelopmental disabilities and cardiovascular diseases. The World Health Organization and United Nations Child’s Fund estimate the prevalence of low birth weights in the world ranges from 3% to 32%. Albania in the year 2000 recorded prevalence of low birth weight of 3% whereas Yemen recorded a low birth weight of 32% in 1997. In 2015, the US national vital statistics pointed out that 83.9% of preterm birth (PTB) are LBW. This indicates that prevention of PTB will lead to a decrease in the incidence of LBW.
    Matched MeSH terms: United States
  11. Fulltext Accidental self-injection of Xylazine during work: a rare case
    Ganapathy, Ganesh Kumar, Dharmalingam, T. Kumaravadivel, Sathival, Mugunthan M.
    Borneo Journal of Medical Sciences, 2018;12(2):47-49.
    MyJurnal
    Xylazine is an alpha-2agonist often used as a sedative, analgesic and muscle relaxant agent
    in animals. Xylazine was not accepted by Food and Drug Administration (FDA) for human use
    due to hazardous side effect such as hypotension, bradycardia, respiratory depression and coma.
    This is a rare case report of a 64-year-old farmer who accidentally injected himself with Xylazine
    which was supposed to be given to a fractious cow. He developed altered conscious level, hypotension, bradycardia and respiratory failure requiring mechanical ventilation. Fortunately, he
    recovered and was discharged home after three days. This occurred due to improper handling of
    Xylazine without standard operating procedures. Xylazine is regulated for animal use only. Therefore, effects of Xylazine toxicity in human must be emphasized for awareness on proper handling as well as for right management of its poisoning incident in future.
    Matched MeSH terms: United States; United States Food and Drug Administration
  12. SARS: current overview, aetiology and epidemiology
    Cavaljuga S, Faulde M, Scharninghausen JJ
    Bosn J Basic Med Sci, 2003 May;3(2):46-55.
    PMID: 16223373
    At this moment, public health authorities, physicians and scientists around the world are struggling to cope with a severe and rapidly spreading new disease in humans called severe acute respiratory syndrome, or SARS. According to World Health Organisation (WHO) this appears to be the first severe and easily transmissible new disease to emerge in the 21st century. Though much about the disease remains poorly understood, including the details of the causative virus, we do know that it has features that allow it to spread rapidly along international air travel routes. As of 10 May 2003, a cumulative 7296 probable SARS cases with 526 deaths have been reported from 30 countries on three continents (WHO, ProMED). In the past week, more than 1000 new probable cases and 96 deaths were reported globally. This represents an increase of 119 new cases and 8 new deaths compared with 9 May 2003 (China (85), Taiwan (23), and Hong Kong (7) represented the overwhelming majority, with one additional case each reported from France, Malaysia, Singapore, and the United States). Only in China, as of 10 May 2003 (WHO) total of 4884 with 235 deaths have been reported. Some outbreaks have reassuring features.
    Matched MeSH terms: United States
  13. Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa
    Ablashi D, Chatlynne L, Cooper H, Thomas D, Yadav M, Norhanom AW, et al.
    Br. J. Cancer, 1999 Nov;81(5):893-7.
    PMID: 10555764
    Seroprevalence of HHV-8 has been studied in Malaysia, India, Sri Lanka, Thailand, Trinidad, Jamaica and the USA, in both healthy individuals and those infected with HIV. Seroprevalence was found to be low in these countries in both the healthy and the HIV-infected populations. This correlates with the fact that hardly any AIDS-related Kaposi's sarcoma has been reported in these countries. In contrast, the African countries of Ghana, Uganda and Zambia showed high seroprevalences in both healthy and HIV-infected populations. This suggests that human herpes virus-8 (HHV-8) may be either a recently introduced virus or one that has extremely low infectivity. Nasopharyngeal and oral carcinoma patients from Malaysia, Hong Kong and Sri Lanka who have very high EBV titres show that only 3/82 (3.7%) have antibody to HHV-8, demonstrating that there is little, if any, cross-reactivity between antibodies to these two gamma viruses.
    Matched MeSH terms: United States/epidemiology
  14. American Brachytherapy Society: Brachytherapy treatment recommendations for locally advanced cervix cancer for low-income and middle-income countries
    Suneja G, Brown D, Chang A, Erickson B, Fidarova E, Grover S, et al.
    Brachytherapy, 2017 Jan-Feb;16(1):85-94.
    PMID: 27919654 DOI: 10.1016/j.brachy.2016.10.007
    PURPOSE: Most cervix cancer cases occur in low-income and middle-income countries (LMIC), and outcomes are suboptimal, even for early stage disease. Brachytherapy plays a central role in the treatment paradigm, improving both local control and overall survival. The American Brachytherapy Society (ABS) aims to provide guidelines for brachytherapy delivery in resource-limited settings.

    METHODS AND MATERIALS: A panel of clinicians and physicists with expertise in brachytherapy administration in LMIC was convened. A survey was developed to identify practice patterns at the authors' institutions and was also extended to participants of the Cervix Cancer Research Network. The scientific literature was reviewed to identify consensus papers or review articles with a focus on treatment of locally advanced, unresected cervical cancer in LMIC.

    RESULTS: Of the 40 participants invited to respond to the survey, 32 responded (response rate 80%). Participants were practicing in 14 different countries including both high-income (China, Singapore, Taiwan, United Kingdom, and United States) and low-income or middle-income countries (Bangladesh, Botswana, Brazil, India, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). Recommendations for modifications to existing ABS guidelines were reviewed by the panel members and are highlighted in this article.

    CONCLUSIONS: Recommendations for treatment of locally advanced, unresectable cervical cancer in LMIC are presented. The guidelines comment on staging, external beam radiotherapy, use of concurrent chemotherapy, overall treatment duration, use of anesthesia, applicator choice and placement verification, brachytherapy treatment planning including dose and prescription point, recommended reporting and documentation, physics support, and follow-up.
    Matched MeSH terms: United States
  15. A Review of Machine Learning Methods of Feature Selection and Classification for Autism Spectrum Disorder
    Rahman MM, Usman OL, Muniyandi RC, Sahran S, Mohamed S, Razak RA
    Brain Sci, 2020 Dec 07;10(12).
    PMID: 33297436 DOI: 10.3390/brainsci10120949
    Autism Spectrum Disorder (ASD), according to DSM-5 in the American Psychiatric Association, is a neurodevelopmental disorder that includes deficits of social communication and social interaction with the presence of restricted and repetitive behaviors. Children with ASD have difficulties in joint attention and social reciprocity, using non-verbal and verbal behavior for communication. Due to these deficits, children with autism are often socially isolated. Researchers have emphasized the importance of early identification and early intervention to improve the level of functioning in language, communication, and well-being of children with autism. However, due to limited local assessment tools to diagnose these children, limited speech-language therapy services in rural areas, etc., these children do not get the rehabilitation they need until they get into compulsory schooling at the age of seven years old. Hence, efficient approaches towards early identification and intervention through speedy diagnostic procedures for ASD are required. In recent years, advanced technologies like machine learning have been used to analyze and investigate ASD to improve diagnostic accuracy, time, and quality without complexity. These machine learning methods include artificial neural networks, support vector machines, a priori algorithms, and decision trees, most of which have been applied to datasets connected with autism to construct predictive models. Meanwhile, the selection of features remains an essential task before developing a predictive model for ASD classification. This review mainly investigates and analyzes up-to-date studies on machine learning methods for feature selection and classification of ASD. We recommend methods to enhance machine learning's speedy execution for processing complex data for conceptualization and implementation in ASD diagnostic research. This study can significantly benefit future research in autism using a machine learning approach for feature selection, classification, and processing imbalanced data.
    Matched MeSH terms: United States
  16. Ten-year survival in women with primary stage IV breast cancer
    Eng LG, Dawood S, Sopik V, Haaland B, Tan PS, Bhoo-Pathy N, et al.
    Breast Cancer Res Treat, 2016 11;160(1):145-152.
    PMID: 27628191
    PURPOSE: To evaluate breast cancer-specific survival at 10 years in patients who present with primary stage IV breast cancer, and to determine whether survival varies with age of diagnosis.

    METHODS: We retrieved the records of 25,323 women diagnosed with primary stage IV breast cancer in the surveillance, epidemiology, and end results 18 registries database from 1990 to 2012. For each case, we extracted information on age at diagnosis, tumour size, nodal status, oestrogen receptor status, progesterone receptor status, ethnicity, cause of death and date of death. The Cox proportional hazards model was used to estimate the unadjusted and adjusted hazard ratio (HR) of death due to stage IV breast cancer, according to age group.

    RESULTS: Among 25,323 women with stage IV breast cancer, 2542 (10.0 %) were diagnosed at age 40 or below, 5562 (22.0 %) were diagnosed between ages 41 and 50 and 17,219 (68.0 %) were diagnosed between ages 51 and 70. After a mean follow-up of 2.2 years, 16,387 (64.7 %) women died of breast cancer (median survival 2.3 years). The ten-year actuarial breast cancer-specific survival rate was 15.7 % for women ages 40 and below, 14.9 % for women ages 41-50 and 11.7 % for women ages 51 to 70 (p 

    Matched MeSH terms: United States/epidemiology
  17. Fulltext Greater absolute risk for all subtypes of breast cancer in the US than Malaysia
    Horne HN, Beena Devi CR, Sung H, Tang TS, Rosenberg PS, Hewitt SM, et al.
    Breast Cancer Res Treat, 2015 Jan;149(1):285-91.
    PMID: 25537643 DOI: 10.1007/s10549-014-3243-9
    Hormone receptor (HR) negative breast cancers are relatively more common in low-risk than high-risk countries and/or populations. However, the absolute variations between these different populations are not well established given the limited number of cancer registries with incidence rate data by breast cancer subtype. We, therefore, used two unique population-based resources with molecular data to compare incidence rates for the 'intrinsic' breast cancer subtypes between a low-risk Asian population in Malaysia and high-risk non-Hispanic white population in the National Cancer Institute's surveillance, epidemiology, and end results 18 registries database (SEER 18). The intrinsic breast cancer subtypes were recapitulated with the joint expression of the HRs (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor-2 (HER2). Invasive breast cancer incidence rates overall were fivefold greater in SEER 18 than in Malaysia. The majority of breast cancers were HR-positive in SEER 18 and HR-negative in Malaysia. Notwithstanding the greater relative distribution for HR-negative cancers in Malaysia, there was a greater absolute risk for all subtypes in SEER 18; incidence rates were nearly 7-fold higher for HR-positive and 2-fold higher for HR-negative cancers in SEER 18. Despite the well-established relative breast cancer differences between low-risk and high-risk countries and/or populations, there was a greater absolute risk for HR-positive and HR-negative subtypes in the US than Malaysia. Additional analytical studies are sorely needed to determine the factors responsible for the elevated risk of all subtypes of breast cancer in high-risk countries like the United States.
    Matched MeSH terms: United States
  18. 'A better alternative': why women use peer-to-peer shared milk
    Gribble KD
    Breastfeed Rev, 2014 Mar;22(1):11-21.
    PMID: 24804519
    The process by which women came to use internet-facilitated peer-to-peer shared milk was explored via a written questionnaire administered to 41 peer milk recipients from five countries. Respondents were universally unable to provide some or all of the milk their infants required. Twenty-nine dyads had a medical condition that could have affected their ability to breastfeed. Many respondents had had great difficulty in finding health workers who could assist them with their breastfeeding challenges. Before obtaining peer-shared milk, respondents had tried to increase their own milk supply, used infant formula or sought donor milk from personal contacts. Health workers dealing with breastfeeding women require greater training in the recognition and treatment of conditions that adversely affect breastfeeding including a physiological incapacity to fully breastfeed. Peer-to-peer milk recipients appear to be very satisfied with the solution milk sharing provides to their problem of being unable to fully breastfeed their infants.
    Matched MeSH terms: United States
  19. Personality traits and learning
    Kohli S, Bhatia S
    Br Dent J, 2021 02;230(4):186.
    PMID: 33637900 DOI: 10.1038/s41415-021-2752-2
    Matched MeSH terms: United States
  20. Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time-series gene expression profiling
    Yeoh AE, Li Z, Dong D, Lu Y, Jiang N, Trka J, et al.
    Br J Haematol, 2018 Jun;181(5):653-663.
    PMID: 29808917 DOI: 10.1111/bjh.15252
    Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under- or over-treatment. We hypothesized that time-series gene expression profiles (GEPs) of bone marrow samples during remission-induction therapy can measure the response and be used for relapse prediction. We computed the time-series changes from diagnosis to Day 8 of remission-induction, termed Effective Response Metric (ERM-D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD). ERM-D8 was trained on a set of 131 patients and validated on an independent set of 79 patients. In the independent blinded test set, unfavourable ERM-D8 patients had >3-fold increased risk of relapse compared to favourable ERM-D8 (5-year cumulative incidence of relapse 38·1% vs. 10·6%; P = 2·5 × 10-3 ). ERM-D8 remained predictive of relapse [P = 0·05; Hazard ratio 4·09, 95% confidence interval (CI) 1·03-16·23] after adjusting for NCI criteria, genetics, Day 8 peripheral response and Day 33 MRD. ERM-D8 improved risk stratification in favourable genetics subgroups (P = 0·01) and Day 33 MRD positive patients (P = 1·7 × 10-3 ). We conclude that our novel metric - ERM-D8 - based on time-series GEP after 8 days of remission-induction therapy can independently predict relapse even after adjusting for NCI risk, genetics, Day 8 peripheral blood response and MRD.
    Matched MeSH terms: United States
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