Long noncoding RNAs (lncRNAs) can promote or repress the cellular hallmarks of cancer.Understanding their molecular roles and realising their therapeutic potential depend on highquality catalogues of cancer lncRNA genes. Presently, such catalogues depend on labourintensive curation of heterogeneous data with permissive criteria, resulting in unknown numbers of genes without direct functional evidence. Here, we present an approach for semiautomated curation focused exclusively on pathogenic functionality. The result is Cancer LncRNA Census 2 (CLC2), comprising 492 gene loci in 33 cancer types. To complement manual literature curation, we develop an automated pipeline, CLIO-TIM, to identify novel cancer lncRNAs based on functional evolutionary conservation with mouse. This yields 95 novel lncRNAs, which display characteristics of known cancer genes and include LINC00570 (ncRNA-a5), which we demonstrate experimentally to promote cell proliferation. The clinical importance and curation accuracy of CLC2 lncRNAs is highlighted by a range of features, including evolutionary selection, expression in tumours, and both somatic and germline polymorphisms. The entire dataset is available in a highly-curated format facilitating the widest range of downstream applications. In summary, we show how manual and automated methods can be integrated to catalogue known and novel functional cancer lncRNAs with unique genomic and clinical properties.

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Tuberculosis (TB) and human immunodeficiency virus (HIV) are the two major public health emergencies in the Philippines. The country is ranked fourth worldwide in TB incidence cases despite national efforts and initiatives to mitigate the disease. Concurrently, the Philippines has the fastest-growing HIV epidemic in Asia and the Pacific region. The TB-HIV dual epidemic forms a lethal combination enhancing each other’s progress, driving the deterioration of immune responses. In order to understand and describe the transmission dynamics and epidemiological patterns of the co-infection, a compartmental model for TB-HIV is developed. A class of people living with HIV (PLHIV) who did not know their HIV status is incorporated into the model. These unaware PLHIV who do not seek medical treatment are potential sources of new HIV infections that could significantly influence the disease transmission dynamics. Sensitivity analysis using the partial rank correlation coefficient is performed to assess model parameters that are influential to the output of interests. The model is calibrated using available Philippine data on TB, HIV, and TB-HIV. Parameters that are identified include TB and HIV transmission rates, progression rates from exposed to active TB, and from TB-latent with HIV to active infectious TB with HIV in the AIDS stage. Uncertainty analysis is performed to identify the degree of accuracy of the estimates. Simulations predict an alarming increase of 180% and 194% in new HIV and TB-HIV infections in 2025, respectively, relative to 2019 data. These projections underscore an ongoing health crisis in the Philippines that calls for a combined and collective effort by the government and the public to take action against the lethal combination of TB and HIV.

1048 Poster Board I-70 Background: Patients with high risk AML, including those with advanced age, relapsed or refractory disease, unfavorable cytogenetics, therapy-related myeloid neoplasm (t-MN), and multiple medical co-morbidities, carry a poor prognosis and outcomes after 7+3 induction chemotherapy are poor. Complete remission (CR) rates tend to be low and range from 12-63% and induction death rates range from 10-26%. We developed a novel, timed-sequential regimen that takes advantage of synergy when MITO follows cytarabine (VW Quinones et al. ASH 1996. abstr 849). Methods: We performed a retrospective analysis of all AML patients, except those with t(15;17), who received HiDAC/MITO from 2001-2008 at our institution. Patients with high risk AML defined by age >60 and/or at least two adverse prognostic features (cytogenetics, co-morbid conditions, antecedent hematologic disorder) received cytarabine at 3gm/m2 over four hours (with dose reduction to 2gm/m2 for patients >60 years old) on days 1 and 5 plus mitoxantrone at 30mg/m2 (with dose reduction to 20mg/m2 for patients >60) over one hour immediately following the HiDAC on days 1 and 5. The primary endpoints of the study were CR and toxicity determined by induction death defined as death within 30 days of initiation of treatment. Results: 78 consecutive patients received HiDAC/MITO for remission induction. The median age was 63 years (range 23-85); 27% of these patients had a Charlson comorbidity index (CCI) >2. The distribution of diagnoses is shown in the Table. 43 (56%) patients had poor-risk cytogenetics, 28 (37%) had intermediate-risk cytogenetics and 5 (7%) had good-risk cytogenetics. Overall CR rate was 45%, CRi rate 10%, refractory rate 36%, and induction death rate of 9%. Patients with AML with myelodysplasia related changes tended to have a lower CR rate (p=0.07) and were more likely to have a CRi. Notably, t-MN and relapsed/refractory patients had CR and induction death rates equivalent to de novo AML patients. Cytogenetics and CCI were also not associated with best response, p=0.7 and 0.94, respectively. Forty percent of patients proceeded to allogeneic stem cell transplantation (alloSCT) after receiving HiDAC/MITO. Overall survival at one year was 39%. Conclusions: In this high risk AML population, HiDAC/MITO induction was well tolerated and demonstrated an overall response rate of 55% and low induction death rate of 9%, allowing a substantial number of patients to proceed to alloSCT. High risk cytogenetics and multiple medical co-morbidities did not affect CR rate, and the CR rate was similar among relapsed/refractory, t-MN and de novo AML patients, which highlights the utility of this regimen for both high risk newly diagnosed and relapsed/refractory patients with AML. Disclosures: No relevant conflicts of interest to declare.