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Acute myeloid leukemia (AML) is a heterogeneous disease, and targeted therapy has been shown to improve the outcomes of AML patients. Recently, we identified a novel G3BP stress granule assembly factor 1 (G3BP1)-colony stimulating factor 1 receptor (CSF1R) fusion gene by RNA sequencing in a patient with acute megakaryoblastic leukemia (AMKL). G3BP1-CSF1R (GC) juxtaposed exon 8 of G3BP1 to exon 12 of CSF1R and was predicted to encode a fusion protein containing the disrupted juxtamembrane domain (JMD) and the intact kinase domain of CSF1R. A similar CSF1R rearrangement has been reported in an AMKL cell line, MKPL1, which harbors the RBM6-CSF1R fusion. As the second CSF1R fusion discovered in AMKL, it remains unclear whether GC is a novel oncogenic driver and whether it is involved in dictating megakaryocytic phenotype. The aim of this study was to characterize the GC fusion and to investigate its role in AMKL pathogenesis and its targetability. Immunofluorescence studies showed that GC and G3BP1 were located in the cytoplasm, unlike the wide-type CSF1R which exhibited vesicular localization. Co-IP studies indicated that GC could exist as dimers in the absence of ligand stimulation. Two cytokine-dependent cell lines (TF1 and M07E) transduced with GC lentivirus showed cytokine-independent growth and constitutive activation of CSF1R and its downstream signaling, indicating the transforming ability of GC. Consistently, NSG mice transplanted with GC-expressing TF1 cells developed AML. In vitro drug studies revealed that GC-transformed TF1 (TF1-GC) and MKPL1 cells were sensitive to dasatinib and pexidartinib, as demonstrated by inhibition of kinase activation, reduced cell proliferation, and increased apoptosis. Moreover, in NSG mice transplanted with TF1-GC cells, dasatinib and pexidartinib significantly decreased leukemia burden and prolonged survival. Using flow cytometry, we observed that GC increased cell size, granularity, and megakaryocytic markers (CD41 and CD61) in M07E, TF1, and human cord blood CD34+ stem and progenitor cells, suggesting that GC could promote megakaryocytic skewing. Taken together, we identified and characterized a novel targetable GC fusion in AMKL. These findings may provide insights into the role of CSF1R in AMKL pathogenesis and a rationale for CSF1R-targeted therapy in AML patients with CSF1R activating alterations. Citation Format: Xi Luo, Chi Keung Cheng, Hoi Yun Chan, Yuet Fong Kam, Kam Tong Leung, Chi Kong Li, Margaret Heung-Ling Ng. A novel targetable G3BP stress granule assembly factor 1 (G3BP1)-colony stimulating factor 1 receptor (CSF1R) fusion in acute megakaryoblastic leukemia (AMKL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3393.

Stuck pipe incidents are one of the contributors to non-productive time (NPT), where they can result in a higher well cost. This research investigates the feasibility of applying machine learning to predict events of stuck pipes during drilling operations in petroleum fields. The predictive model aims to predict the occurrence of stuck pipes so that relevant drilling operation personnel are warned to enact a mitigation plan to prevent stuck pipes. Two machine learning methodologies were studied in this research, namely, the artificial neural network (ANN) and support vector machine (SVM). A total of 268 data sets were successfully collected through data extraction for the well drilling operation. The data also consist of the parameters with which the stuck pipes occurred during the drilling operations. These drilling parameters include information such as the properties of the drilling fluid, bottom-hole assembly (BHA) specification, state of the bore-hole and operating conditions. The R programming software was used to construct both the ANN and SVM machine learning models. The prediction performance of the machine learning models was evaluated in terms of accuracy, sensitivity and specificity. Sensitivity analysis was conducted on these two machine learning models. For the ANN, two activation functions—namely, the logistic activation function and hyperbolic tangent activation function—were tested. Additionally, all the possible combinations of network structures, from [19, 1, 1, 1, 1] to [19, 10, 10, 10, 1], were tested for each activation function. For the SVM, three kernel functions—namely, linear, Radial Basis Function (RBF) and polynomial—were tested. Apart from that, SVM hyper-parameters such as the regularization factor (C), sigma (σ) and degree (D) were used in sensitivity analysis as well. The results from the sensitivity analysis demonstrate that the best ANN model managed to achieve an 88.89% accuracy, 91.89% sensitivity and 86.36% specificity, whereas the best SVM model managed to achieve an 83.95% accuracy, 86.49% sensitivity and 81.82% specificity. Upon comparison, the ANN model is the better machine learning model in this study because its accuracy, sensitivity and specificity are consistently higher than those of the best SVM model. In conclusion, judging from the promising prediction accurateness as demonstrated in the results of this study, it is suggested that stuck pipe prediction using machine learning is indeed practical.

Supplementary Methods. Selection of “best cases and controls” for subset analysis correlating assay readouts with severe late xerostomia. Table S1. Intraclass correlation coefficient (ICC) for additional sensitivity analysis of FLICA measurements. The single measurement and average of 3 measurements columns reports the ICC when either one or three tests were performed, respectively. Table S2. Summary of inter-patient heterogeneity in apoptotic and DNA damage responses. Table S3. Clinical and dosimetric characteristics of the 17 patients included in the sub-group exploratory analysis correlating assay readouts with severe late xerostomia using a “best case-control” design. Figure S1. Gating of (A) general lymphocyte population and (B) CD4+ or CD8+ lymphocyte sub-populations for FLICA apoptosis analysis by flow cytometry. Figure S2. Bland-Altman plots for (A) FLICA assay, and (B) γH2AX for the general lymphocyte population, as well as plots for FLICA assays of the (C) CD4+ and (D) CD8+ T lymphocyte subset populations. From Bland-Altman plots, outliers were identified and excluded from subsequent sensitivity analyses. Figure S3. Correlation between background %FLICA and %FLICA post-8 Gy for the (A) CD4 and (B) CD8 T-lymphocyte subsets. Solid lines were generated by linear regression; R values were generated by Spearman correlation test. Figure S4. Apoptotic responses post-8Gy in the CD4 and CD8 T-lymphocyte subsets were correlated for the same patient. Solid lines were generated by linear regression; R values were generated by Spearman correlation test. Figure S5. Sub-group exploratory analysis comparing residual γH2AX 4 Gy 24 h foci count between best cases (N = 9) and controls (N = 8). (PDF 5363 kb)

A1 Hope and despair in the current treatment of nasopharyngeal cancer, IB Tan, I1 NPC international incidence and risk factors, Ellen T Chang, I2 Familial nasopharyngeal carcinoma and the use of biomarkers, Chien-Jen Chen, Wan-Lun Hsu, Yin-Chu Chien, I3 Genetic susceptibility risk factors for sporadic and familial NPC: recent findings, Allan Hildesheim, I5 Genetic and environmental risk factors for nasopharyngeal cancer in Southeast Asia, James D McKay, Valerie Gaborieau, Mohamed Arifin Bin Kaderi, Dewajani Purnomosari, Catherine Voegele, Florence LeCalvez-Kelm, Graham Byrnes, Paul Brennan, Beena Devi, I6 Characterization of the NPC methylome identifies aberrant epigenetic disruption of key signaling pathways and EBV-induced gene methylation, Li L, Zhang Y, Fan Y, Sun K, Du Z, Sun H, Chan AT, Tsao SW, Zeng YX, Tao Q, I7 Tumor exosomes and translational research in NPC, Pierre Busson, Claire Lhuillier, Olivier Morales, Dhafer Mrizak, Aurore Gelin, Nikiforos Kapetanakis, Nadira Delhem, I8 Host manipulations of the Epstein-Barr virus EBNA1 protein, Sheila Mansouri, Jennifer Cao, Anup Vaidya, and Lori Frappier, I9 Somatic genetic changes in EBV-associated nasopharyngeal carcinoma, Lo Kwok Wai, I10 Preliminary screening results for nasopharyngeal carcinoma with ELISA-based EBV antibodies in Southern China, Sui-Hong Chen, Jin-lin Du, Ming-Fang Ji, Qi-Hong Huang, Qing Liu, Su-Mei Cao, I11 EBV array platform to screen for EBV antibodies associated with NPC and other EBV-associated disorders, Denise L. 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Messick, Kimberly Malecka, Lois Tolvinski, Samantha Soldan, Julianna Deakyne, Hui Song, Antonio van den Heuvel, Baiwei Gu, Joel Cassel, Mark McDonnell, Garry R Smith, Venkata Velvadapu, Haiyan Bian, Yan Zhang, Marianne Carlsen, Shuai Chen, Alastair Donald, Christian Lemmen, Allen B Reitz, Paul M Lieberman, O11 Therapeutic targeting of cancer stem-like cells using a Wnt modulator, ICG-001, enhances the treatment outcome of EBV-positive nasopharyngeal carcinoma, King Chi Chan, Lai Sheung Chan, Kwok Wai Lo, Timothy Tak Chun Yip, Roger Kai Cheong Ngan, Michael Kahn, Maria Li Lung, Nai Ki Mak, O12 Role of micro-RNA in NPC biology, Fei-Fei Liu, O13 Expansion of EBNA1- and LMP2-specific effector T lymphocytes from patients with nasopharyngeal carcinoma without enhancement of regulatory T cells, Wafa Khaali; Juliette Thariat; Laurence Fantin; Flavia Spirito; Meriem Khyatti; El Khalil Ben Driss; Sylvain Olivero; Janet Maryanski; Alain Doglio, O14 The experience of patients’ life after amifostine radiotherapy treatment (ART) for nasopharyngeal carcinoma (NPC), Mengxue Xia, Yunfei Xia, Hui Chang, Rachel Shaw, O15 Analysis of mitochondrial DNA mutation in latent membrane protein-1 positive nasopharyngeal carcinoma, Pudji Rahaju, O16 Factors influencing treatment adherence of nasopharyngeal cancer and the clinical outcomes: a hospital-based study, Mardiah Suci Hardianti, Sindhu Wisesa, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda, O17 Chromosomal breaks mediated by bile acid-induced apoptosis in nasopharyngeal epithelial cells: in relation to matrix association region/scaffold attachment region, Sang-Nee Tan, Sai-Peng Sim, O18 Expression of p53 (wild type) on nasopharyngeal carcinoma stem cell that resistant to radiotherapy, Muhtarum Yusuf, Ahmad C Romdhoni, Widodo Ario K, Fedik Abdul Rantam, O19 Mathematical model of nasopharyngeal carcinoma in cellular level, Sugiyanto, Lina Aryati, Fajar Adi-Kusumo, Mardiah Suci Hardianti, O20 Differential expression of microRNA-21 on nasopharyngeal carcinoma plasma patient, SY Bintoro, R Oktriani, C. Herawati, A Surono, Sofia M. Haryana, O21 Therapeutic targeting of an oncogenic fibroblast growth factor-FGF19, which promotes proliferation and induces EMT of carcinoma cells through activating ERK and AKT signaling, L. Zhong, L. Li, B. B. Ma, A. T. Chan, Q. Tao, O22 Resist nasopharyngeal carcinoma (NPC): next generation T cells for the adoptive immunotherapy of NPC, M. Kalra, M. Ngo, S. Perna, A. Leen, N. Lapteva, C. M. Rooney, S. Gottschalk, O23 The correlation of heat shock protein 70 expressions and staging of nasopharyngeal carcinoma, Elida Mustikaningtyas, Sri Herawati, Achmad C Romdhoni, O24 Epstein-Barr virus serological profiles of nasopharyngeal carcinoma - A tribute to Werner Henle, Mingfang Ji, YaruiXu, Weimin Cheng, ShengxiangGe, Fugui Li, M. H. 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Baning Rahayudjati, P3 Report on loco regionally advanced nasopharyngeal cancer patients treated with induction chemotherapy followed by concurrent chemo-radiation therapy, Iswandi Darwis, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P4 Sex and age differences in the survival of patients with nasopharyngeal carcinoma, Sindhu Wisesa, Mardiah Suci Hardianti, Susanna Hilda Hutajulu, Kartika Widayati Taroeno-Harijadi, Ibnu Purwanto, Camelia Herdini, Wigati Dhamiyati, Johan Kurnianda, P5 Impact of delayed diagnosis and delayed therapy in the treatment outcome of patients with nasopharyngeal carcinoma, Khoirul Anwar, Susanna Hilda Hutajulu, Sagung Rai Indrasari, Sri Retna Dwidanarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P6 Anaysis of pretreatment anemia in nasopharyngeal cancer patients undergoing neoadjuvant therapy, Dominicus Wendhy Pramana, Susanna Hilda Hutajulu, Bambang Hariwiyanto, Wigati Dhamiyati, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P7 Results of treatment with neoadjuvant cisplatin-5FU in locally advanced nasopharyngeal carcinoma: a local experience, Diah Ari Safitri, Susanna Hilda Hutajulu, Camelia Herdini, Sri Retna Dwi Danarti, Ibnu Purwanto, Kartika Widayati Taroeno-Hariadi, Johan Kurnianda, P8 Geriatrics with nasopharyngeal cancer, Suryo A Taroeno, Sindhu Wisesa, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Bambang Hariwiyanto, Wigati Dhamiyati, Johan Kurnianda, P9 Correlation of lymphocyte to monocyte and neutrophil to lymphocyte ratio to the response of cisplatin chemoradiotheraphy in locally advance nasopharyngeal carcinoma, I. Wijaya, A. Oehadian, D. Prasetya, P10 Prediction of nasopharyngeal carcinoma risk by Epstein-Barr virus seromarkers and environmental co-factors: the gene-environment interaction study on nasopharyngeal carcinoma in Taiwan, Wan-Lun Hsu, Yin-Chu Chien, Kelly J Yu, Cheng-Ping Wang, Ching-Yuan Lin, Yung-An Tsou, Yi-Shing Leu, Li-Jen Liao, Yen-Liang Chang191,192, Jenq-Yuh Ko, Chun-Hun Hua, Ming-Shiang Wu, Chu-Hsing Kate Hsiao, Jehn-Chuan Lee, Ming-Hsui Tsai, Skye Hung-Chun Cheng, Pei-Jen Lou, Allan Hildesheim, Chien-Jen Chen, P11 Non-viral risk factors for nasopharyngeal carcinoma in West Sumatra, Indonesia, Sukri Rahman, Bestari J. Budiman, Novialdi, Rahmadona, Dewi Yuri Lestari, P12 New prototype Vidas EBV IgA quick: performance on Chinese and Moroccan populations, C. Yin, A. Foussadier, E. Blein, C. Chen, N. Bournet Ammour, M. Khiatti, S. Cao, P13 The expression of EBV-LMP1 and VEGF as predictors and plasma EBV-DNA levels as early marker of distant metastasis after therapy in nasopharyngeal cancer, Dewi Syafriyetti Soeis Marzaini, P14 Characteristics and factors influencing subjects refusal for blood samples retrieval: lesson from NPC case control study in Yogyakarta – Indonesia, Dwi Hartati, Baning Rahayujati, Camelia Herdini, Jajah Fachiroh, P15 Expression of microRNA BART-7-3p and mRNA PTEN on blood plasma of patients with nasopharyngeal carcinoma, L. Gunawan, S. Mubarika Haryana, A. Surono, C. Herawati, P16 IgA response to native early antigen (IgA-EAext) of Epstein-Barr virus (EBV) in healthy population and nasopharyngeal carcinoma (NPC) patients: the potential for diagnosis and screening tools, Michael Hartono, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita, P17 IgA responses against Epstein-Barr Virus Early Antigen (EBV-EA) peptides as potential candidates of nasopharyngeal carcinoma detection marker, Akmal Akbar, Jajah Fachiroh, Dewi Kartikawati Paramita, P18 Association between smoking habit and IgA-EBV titer among healthy individuals in Yogyakarta, Indonesia, Benny Hermawan, T Baning Rahayudjati, Dewi K Paramita, Jajah Fachiroh, P19 Epstein-Barr virus IgA titer comparison of healthy non-family individuals and healthy first degree family of NPV patients, Gabriella Argy, Jajah Fachiroh, Dewi Kartikawati Paramita, Susanna Hilda Hutajulu, P20 Identification of EBV Early Antigen (EA) derived peptides for NPC diagnosis, Theodora Caroline Sihotang, Jajah Fachiroh, Umi Intansari, Dewi Kartikawati Paramita, P21 Host-pathogen study: relative expression of mRNA BRLF1 Epstein-Barr virus as a potential biomarker for tumor progressivity and polymorphisms of TCRBC and TCRGC2 host genes related to genetic susceptibility on nasopharyngeal carcinoma, Daniel Joko Wahyono, Purnomo Soeharso, Dwi Anita Suryandari, Lisnawati, Zanil Musa, Bambang Hermani, P22 In vitro efficacy of silvestrol and episilvestrol, isolated from Borneo, on nasopharyngeal carcinoma, a major cancer in Borneo, Maelinda Daker, Yeo Jiun Tzen, Norhasimah Bakar, Asma’ Saiyidatina Aishah Abdul Rahman, Munirah Ahmad, Yeo Tiong Chia, Alan Khoo Soo Beng, P23 The expression of mir-141 in patients with nasopharyngeal cancer, Widyandani Sasikirana, Tirta Wardana, Muhammad Radifar, Cita Herawati, Agus Surono, Sofia Mubarika Haryana