Editorial Material
Hematology
Qian-Fei Wang, Hong -Hu Zhu
Summary: In this study, Poplineau et al identified a retinoic acid resistance network involving the E2F-EZH2 axis in a PLZF-RARA transgenic acute promyelocytic leukemia mouse model. They demonstrated that the nonenzymatic activity of EZH2 is crucial for retinoic acid resistance. Targeting the pan-EZH2 activity significantly improved survival in mice reconstituted with retinoic acid-resistant PLZF-RARA leukemia cells.
Article
Oncology
Yu Zheng, Yuan-Fei Mao, Hui-Jin Zhao, Li Chen, Li-Ning Wang, Yun-Xiang Zhang, Jiong Hu, Jun-Min Li, Xiao-Yang Li, Hong-Ming Zhu
Summary: This study investigated the arsenic metabolism in APL patients who completed ATO treatment and found a decreased arsenic methylation capacity after treatment. The increased proportion of iAs(III) in urine was associated with chronic liver toxicity, highlighting the importance of monitoring urine PMI and considering SNPs of the AS3MT gene in determining ATO dosage.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Review
Chemistry, Medicinal
Guangzhi Liu, Yurong Song, Chenxi Li, Rui Liu, Youwen Chen, Liuchunyang Yu, Qingcai Huang, Dongjie Zhu, Cheng Lu, Xue Yu, Cheng Xiao, Yuanyan Liu
Summary: Arsenic and its compounds have been utilized for nearly 4000 years, showing important therapeutic roles in treating diseases like acute promyelocytic leukemia. However, long-term exposure to arsenic may have detrimental health effects, particularly carcinogenesis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Zhuo Zhang, Shunji Zhang, Fan Zhang, Qian Zhang, Hong Wei, Ruolin Xiu, Yanhong Zhao, Meijuan Sui
Summary: This study aimed to explore noninvasive clinical indicators that can guide the individualized use of arsenic trioxide (ATO) in the future. The results revealed that hemoglobin >= 80 g/L, nonprophylactic hepatoprotective agents, non-single-agent ATO, and decreased fibrinogen < 1 g/L were risk factors for ATO-induced hepatotoxicity in newly diagnosed APL patients.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Meihua Guo, Qilei Zhao, Shengjin Fan, Zhiqiang Wu, Liwang Lin, Hongzhu Chen, Yanhui Gao, Xin Hai
Summary: The study indicated that APL patients had low total arsenic levels in the CSF, but infusion of mannitol could increase arsenic concentrations in the CSF, improving treatment efficacy.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Jian Lv, Mengliang Wu, Chunrong Pang, Rui Duan, Hong Zhang, Shuo Tian, Haixia Yang, Xin Hai
Summary: Torsemide increased the plasma concentrations of arsenic metabolites in APL patients treated with ATO by inhibiting the transporter MRP4 in a dose-dependent manner. This effect was also observed in rats treated with both ATO and torsemide. Torsemide reduced the excretion of arsenic in urine and increased its concentration in the kidneys of rats.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Li Chen, Hong-Ming Zhu, Yan Li, Qi-Fa Liu, Yu Hu, Jian-Feng Zhou, Jie Jin, Jian-Da Hu, Ting Liu, De-Pei Wu, Jie-Ping Chen, Yong-Rong Lai, Jian-Xiang Wang, Juan Li, Jian-Yong Li, Xin Du, Xin Wang, Ming-Zhen Yang, Jin-Song Yan, Gui-Fang Ouyang, Li Liu, Ming Hou, Xiao-Jun Huang, Xiao-Jing Yan, Dan Xu, Wei-Ming Li, Deng-Ju Li, Yin-Jun Lou, Zheng-Jun Wu, Ting Niu, Ying Wang, Xiao-Yang Li, Jian-Hua You, Hui-Jin Zhao, Yu Chen, Yang Shen, Qiu-Sheng Chen, Jian Li, Bing-Shun Wang, Wei-Li Zhao, Jian-Qing Mi, Kan-Kan Wang, Jiong Hu, Zhu Chen, Sai-Juan Chen, Jun-Min Li
Summary: This study found that the combination of all-trans retinoic acid and arsenic trioxide in treating acute promyelocytic leukemia during consolidation therapy is not inferior to traditional chemotherapy regimens and shows better outcomes in reducing relapse and toxicity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Junfen Xu, Yuanming Shen, Conghui Wang, Sangsang Tang, Shiyuan Hong, Weiguo Lu, Xing Xie, Xiaodong Cheng
Summary: Combination therapy of PARP inhibitors and arsenic compound shows significant therapeutic effects in HR-proficient ovarian cancer, including suppression of cell proliferation, induction of DNA damage, and promotion of apoptosis.
CELL DEATH DISCOVERY
(2021)
Article
Environmental Sciences
Mengliang Wu, Chunrong Pang, Shengwen Lu, Thomas H. Hostetter, Xin Hai
Summary: Our study investigated the impact of type 2 diabetes (T2DM) on arsenic metabolism in acute promye-locytic leukemia (APL) patients treated with arsenic trioxide. We discovered that APL patients with T2DM had significantly higher concentrations of arsenic metabolites compared to non-diabetic patients, and this increase was positively correlated with blood glucose levels. Additionally, APL patients with T2DM were more susceptible to liver injury and QTc interval prolongation due to altered arsenic methylation capacity. In in vitro experiments, we cultured HEK293T cells under different glucose concentrations and observed higher concentrations of arsenic metabolites in cells with high glucose. Moreover, high glucose levels significantly increased the expression of the arsenic uptake transporter AQP7 in HEK293T cells at the mRNA and protein levels. Overall, our study demonstrated that T2DM can lead to elevated concentrations of arsenic metabolites in APL patients by increasing AQP7 expression.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Meihua Guo, Jin Zhou, Shengjin Fan, Limin Li, Hongzhu Chen, Liwang Lin, Qilei Zhao, Xinyu Wang, Wensheng Liu, Zhiqiang Wu, Xin Hai
Summary: The study highlights the importance of monitoring arsenic concentrations in APL patients treated with ATO, and identifies factors influencing arsenic species levels. The C-trough of plasma arsenic species has predictive value for treatment efficacy, which is critical in optimizing ATO therapy outcomes.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2021)
Article
Hematology
Siyuan Xu, Siqing Wang, Shenghui Xing, Dingdang Yu, Bowen Rong, Hai Gao, Mengyao Sheng, Yun Tan, Xiaojian Sun, Kankan Wang, Kai Xue, Zhennan Shi, Fei Lan
Summary: Epigenetic abnormalities play a critical role in cancer, specifically in diseases like AML where aberrant fusion proteins drive the disease. The loss of KDM5A leads to differentiation and growth retardation in APL NB4 cells, by suppressing the expression of key target genes. Inhibition of KDMSA could greatly enhance differentiation in NB4 cells, suggesting a potential therapeutic target in APL treatment.
Article
Oncology
Yanfeng Liu, Yan Jia, Yi Liu, Xuefeng Chen, Mei Zhang
Summary: This study confirms the potential of tetra-arsenic tetra-sulfide (As4S4) as an adjuvant for NK-92MI in the treatment of ATRA-resistant APL.
INVESTIGATIONAL NEW DRUGS
(2022)
Article
Pharmacology & Pharmacy
Shiyi Xu, Xinyu Zhang, Xingyu Zhu, Hui Su, Xueying Yan
Summary: Co-loading nanoparticle encapsulation is an effective strategy for anti-tumor treatment. The combination of arsenic trioxide and tetrandrine synergistically inhibits tumor growth and metastasis. This study developed co-loading nanoparticle formulations and demonstrated their improved drug distribution and anti-tumor activity.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Toxicology
Chunlu Gao, Liwang Lin, Jing Li, Mengliang Wu, Jian Lv, Shuo Tian, Xin Hai
Summary: This study identifies the binding sites of arsenic on hemoglobin in acute promyelocytic leukemia (APL) patients after arsenic trioxide (As2O3) treatment. Arsenic accumulates in erythrocytes by binding to Cys-104 alpha and Cys-112 beta in hemoglobin. Understanding this interaction could contribute to the therapeutic effect of As2O3 as an anticancer drug and its toxicity on APL patients.
TOXICOLOGY LETTERS
(2023)
Article
Oncology
Cristina M. Ghiuzeli, Miroslav Styblo, Jesse Saunders, Anthony Calabro, Daniel Budman, Steven Allen, Craig Devoe, Radhika Dhingra
Summary: The study found that the metabolism of arsenic trioxide (ATO) in patients with Acute Promyelocytic Leukemia (APL) is influenced by smoking and previous chemotherapy exposure. Different patients exhibited distinct patterns of iAs metabolism, which could impact the effective dose of ATO.
LEUKEMIA & LYMPHOMA
(2022)
Article
Hematology
Sharon Anbumalar Lionel, Sushil Selvarajan, Anu Korula, Uday Kulkarni, Anup Devasia, Fouzia N. N. Abubacker, Aby Abraham, Vikram Mathews, Kavitha M. M. Lakshmi, Biju George
Summary: Immunosuppressive therapy using ATG and CSA improves blood counts in patients with aplastic anemia. Infections are the most lethal complication of this disease. This study aimed to determine the prevalence and predictors of specific infection types before and after IST. The results showed that infections were highest in the six months post-IST, especially in patients with severe aplastic anemia and those who did not respond to ATG. The highest mortality was observed when both bacterial and fungal infections were present.
INDIAN JOURNAL OF HEMATOLOGY AND BLOOD TRANSFUSION
(2023)
Review
Immunology
Balaji Balakrishnan, Uday Prakash Kulkarni, Aswin Anand Pai, Raveen Stephen Stallon Illangeswaran, Ezhilpavai Mohanan, Vikram Mathews, Biju George, Poonkuzhali Balasubramanian
Summary: Hematopoietic cell transplantation (HCT) is an effective treatment for hematological diseases, but early complications such as GVHD and SOS limit its success. Research has focused on discovering blood-based biomarkers to diagnose and predict complications and therapy response. However, these biomarkers are not yet used in routine clinical practice. This review summarizes the biomarkers for early complications post-HCT, ongoing trials, and challenges in using them.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Surgery
Biju George, Rajesh Balakrishnan, S. Patricia, Sharon Lionel, Sushil Selvarajan, Anup J. Devasia, Anu Korula, Kavitha M. Lakshmi, Fouzia N. Aboobacker, Uday Kulkarni, Henry Finlay Godson, Jose Solomon Raj, Aby Abraham, Selvamani Backianathan, Vikram Mathews
Summary: Total marrow lymphoid irradiation (TMLI) can deliver higher doses of irradiation without increasing toxicity, and the combination of TMLI and cyclophosphamide for myeloablative conditioning is associated with low toxicity and favorable early outcomes in patients undergoing hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia with lymphoid blast crises (CML-LBC).
CLINICAL TRANSPLANTATION
(2023)
Article
Genetics & Heredity
Gaurav Joshi, Nancy Beryl Janet Arthur, Thenral S. Geetha, Phaneendra Venkateswara Rao Datari, Kirti Modak, Debanjan Roy, Anurag Dutta Chaudhury, Prasanth Sundaraganesan, Sweety Priyanka, N. A. Fouzia, Vedam Ramprasad, Aby Abraham, Vivi M. Srivastava, Alok Srivastava, Uday Prakash Kulkarni, Biju George, Shaji R. Velayudhan
Summary: A comprehensive analysis of cellular and molecular tests was performed on 142 Indian patients with Fanconi anaemia (FA). A new algorithm for rapid and cost-effective molecular diagnosis of FA was established, which can accurately diagnose approximately 90% of cases.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Raveen Stephen Stallon Illangeswaran, Daniel Zechariah Paul Jebanesan, Kezia Kanimozhi Sivakumar, Rakhi Thalayattu Vidhyadharan, Bharathi M. Rajamani, Nancy Beryl Janet, Ernest David, Shaji Ramachandran Velayudhan, Vikram Mathews, Poonkuzhali Balasubramanian
Summary: Chemotherapy resistance in acute myeloid leukemia (AML) is a significant barrier, and metabolic adaptations play a role in therapy resistance. Our study established cytarabine-resistant and arsenic trioxide-resistant AML cell lines with distinct metabolic profiles. AraC-R cells rely on OXPHOS, while ATO-R cells rely on glycolysis. AraC-R cells are also less stem-like compared to ATO-R cells. The different metabolic dependencies of these cells can be targeted for chemotherapy-resistant AML treatment.
Letter
Oncology
Uday Prakash Kulkarni, Sushil Selvarajan, N. A. Fouzia, Sharon Lionel, Sukesh Chandran Nair, Poonkuzhali Balasubramanian, Thenmozhi Mani, Aby Abraham, Biju George, Vikram Mathews
BLOOD CANCER JOURNAL
(2023)
Article
Microbiology
Abi Manesh Sathya Kumar, Mithun Mohan George, Kundakarla Bhanuprasad, Grace Mary John, Anu Korula, Aby Abraham, Vikram Mathews, Uday Prakash Kulkarni, Chaitra Shankar, Prasanna Samuel Premkumar, Binila Chacko, K. Subramani, George M. Varghese, V. Balaji, Biju George
Summary: This study evaluated the role of follow-up blood cultures (FUBC) positivity in predicting outcomes among patients with neutropenia and carbapenem-resistant gram-negative bloodstream infections (CRGNBSI). Among the 155 patients in the study cohort, the 30-day mortality rate was 47.7%, and 43.8% of patients had persistent bacteremia. Patients with persistent bacteremia had a higher mortality rate compared to those without.
ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS
(2023)
Article
Pharmacology & Pharmacy
Bharathi M. Rajamani, Raveen Stephen Stallon Illangeswaran, Esther Sathya Bama Benjamin, Balaji Balakrishnan, Daniel Zechariah Paul Jebanesan, Saswati Das, Aswin Anand Pai, Rakhi Thalayattu Vidhyadharan, Ajith Mohan, Sreeja Karathedath, Aby Abraham, Vikram Mathews, Shaji R. Velayudhan, Poonkuzhali Balasubramanian
Summary: This study identified that Retinoid-X-receptor alpha (RXRA), a ligand-activated transcription factor, was downregulated in imatinib mesylate (IM)-resistant chronic myeloid leukemia (CML) cell lines and primary CML patient samples. Pre-treatment with RXRA agonists improved sensitivity to IM in vitro and reduced leukemic burden and prolonged survival in vivo. Overexpression of RXRA inhibited proliferation and improved sensitivity to IM both in vitro and in vivo. Combining IM with RXRA ligands may serve as an alternative treatment strategy for CML patients with suboptimal response to IM.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Oncology
Madhavi Maddali, Arun Kumar Arunachalam, Alpesh Kumar BipinBhai Kapadia, Uday Prakash Kulkarni, Poonkuzhali Balasubramanian
Summary: The diagnostic evaluation of myeloproliferative neoplasms (MPNs) relies on clinical features, bone marrow biopsy, and molecular markers. MPNs often have driver mutations in genes like JAK2, CALR, or MPL, as well as mutations related to epigenetic regulation, RNA splicing, and signaling. These mutations are important for diagnosing, prognosticating, and treating MPNs. Molecular characterization is necessary for supporting diagnoses or confirming entities defined by underlying molecular abnormalities. A structured molecular analysis workflow is essential for a prompt and cost-effective diagnosis of MPN. This review explores the role of molecular diagnostics in assessing BCR::ABL1-negative MPNs.
INDIAN JOURNAL OF MEDICAL AND PAEDIATRIC ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Aswin Anand Pai, Ezhilpavai Mohanan, John C. Panetta, Uday P. Kulkarni, Raveen Stephen Stallon Illangeswaran, Balaji Balakrishnan, Agila Jayaraman, Eunice S. Edison, Kavitha M. Lakshmi, Anup J. Devasia, Nambiathayil Aboobacker Fouzia, Anu Korula, Aby Abraham, Biju George, Alok Srivastava, Vikram Mathews, Joseph F. Standing, Poonkuzhali Balasubramanian
Summary: A new chemotherapy regimen has significantly improved hematopoietic stem cell transplantation outcomes for patients with high-risk beta-thalassemia major, but complications still exist. A study on the dose-exposure-response relationship of treosulfan reveals that lower exposure increases the risk of graft rejection and early transplant-related mortality. Therapeutic drug monitoring-based dose adjustment may be beneficial.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Medical Laboratory Technology
Arun Kumar Arunachalam, Sushil Selvarajan, Thenmozhi Mani, Nancy Beryl Janet, Madhavi Maddali, Sharon Anbumalar Lionel, Uday Kulkarni, Anu Korula, Fouzia N. Aboobacker, Aby Abraham, Biju George, Poonkuzhali Balasubramanian, Vikram Mathews
Summary: This retrospective study evaluated the prognostic relevance of measurable residual disease (MRD) at the end of induction in B-cell acute lymphoblastic leukemia (B ALL) patients. The study found that end of induction MRD value and baseline karyotype were the strongest predictors of prognosis. Patients who were MRD positive had poorer outcomes compared to those who were MRD negative, regardless of age, karyotype, BCR::ABL1 translocation, and treatment protocol. These findings contribute to the development of MRD-based treatment guidelines for B ALL patients.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Multidisciplinary Sciences
Amal Paul, Uday Kulkarni, Bijesh Yadav, Fouzia N. Aboobacker, Anup J. Devasia, Anu Korula, Aby Abraham, Biju George, Paul V. George, Alok Srivastava
Summary: The study aimed to assess the prevalence and predictors of subclinical left ventricular dysfunction in an apparently normal population of ex-thalassaemic patients, and found a high prevalence of subclinical myocardial dysfunction, emphasizing the need for close follow up of these patients.
Article
Multidisciplinary Sciences
Balaji Balakrishnan, Raveen Stephen Stallon Illangeswaran, Bharathi Murugan Rajamani, Arun Kumar Arunachalam, Aswin Anand Pai, Ezhilpavai Mohanan, Alok Srivastava, Vikram Mathews, Poonkuzhali Balasubramanian
Summary: The toxicity profiles of busulfan and treosulfan in endothelial cells were investigated. Busulfan induced oxidative stress and apoptosis, while treosulfan did not. Metformin effectively ameliorated busulfan-mediated toxicity in endothelial cells.
Article
Cell & Tissue Engineering
Uday Kulkarni, Arun Kumar Arunachalam, Hamenth Kumar Palani, Reeshma Radhakrishnan Nair, Nithya Balasundaram, Arvind Venkatraman, Anu Korula, Sushil Selvarajan, Sharon Lionel, Poonkuzhali Balasubramanian, Madhavi Maddali, Aby Abraham, Biju George, Vikram Mathews
Summary: Refractory acute myeloid leukemia (AML) is a subgroup with poor outcomes. Haploidentical natural killer cell (NK) therapy is being explored as a strategy in refractory malignancies. In a trial, CD56-positive cells from a family donor were infused into patients, and it was found that this treatment approach had certain survival advantages for patients with refractory AML.
CELL TRANSPLANTATION
(2023)