Review
Oncology
Andrei Colita, Alina Daniela Tanase, Ciprian Tomuleasa, Anca Colita
Summary: Acute promyelocytic leukemia (APL) patients who relapse, despite treatment with all-trans retinoic acid and arsenic trioxide, require a highly efficient consolidation treatment. Hematopoietic stem cell transplantation is recommended for these patients. However, there are still controversies regarding the role of transplantation in APL and further studies are needed.
Article
Oncology
Xiaojing Lin, Niu Qiao, Yang Shen, Hai Fang, Qing Xue, Bowen Cui, Li Chen, Hongming Zhu, Sujiang Zhang, Yu Chen, Lu Jiang, Shengyue Wang, Junmin Li, Bingshun Wang, Bing Chen, Zhu Chen, Saijuan Chen
Summary: This study conducted a systematic analysis of genomics and transcriptomics of APL patients to develop a new scoring system (APL9 score), which, combined with NRAS mutations and WBC counts, stratified patients into two groups, with the revised standard-risk group showing significantly better survival rates.
CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Jaime Sanz, Pau Montesinos, Miguel A. Sanz
Summary: The historical evolution of hematopoietic stem cell transplantation (HSCT) in acute promyelocytic leukemia (APL) has shifted from widespread use to rejection in modern treatments, with ATO-based regimens now considered the first option for relapsed cases. The use of HSCT depends on variables such as pre-transplant molecular status and age, and recent studies have questioned the superiority of HSCT over other consolidation options, suggesting the need for further research.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Xuzhao Zhang, Jinliang Chen, Weiqin Wang, Xian Li, Yanbin Tan, Xiaohong Zhang, Wenbin Qian
Summary: Extramedullary relapse of acute promyelocytic leukemia is rare and associated with poor prognosis, with limited current treatment options. Venetoclax, a BCL2 inhibitor, shows potential in treating central nervous system relapse, providing a new treatment option for patients with this condition.
FRONTIERS IN ONCOLOGY
(2021)
Review
Hematology
Masamitsu Yanada
Summary: The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has greatly improved the outcomes of acute promyelocytic leukemia (APL). ATO-based therapy has shown high rates of hematological and molecular complete remission (CR) in relapsed APL. Autologous hematopoietic cell transplantation (HCT) is the preferred post-remission therapy for patients who achieve molecular CR, while allogeneic HCT is reserved for selected patients who cannot achieve CR or relapse after autologous HCT. Prolonged administration of ATRA + ATO is an option for patients ineligible for HCT.
ANNALS OF HEMATOLOGY
(2022)
Article
Hematology
Huibo Li, Jinxiao Hou, Yueyue Fu, Yanqiu Zhao, Jie Liu, Dan Guo, Ruiqi Lei, Yiting Wu, Linqing Tang, Shengjin Fan
Summary: Treatment with arsenic trioxide (ATO) effectively prolongs the overall survival of patients with acute promyelocytic leukemia (APL). This study identified different microRNA expression patterns between newly diagnosed and relapsed APL patients, with miR-603 being expressed at the lowest level in relapsed patients. miR-603 directly targets tropomyosin-related kinase B (TrkB) and downregulates its expression in APL cells, promoting cell proliferation by inhibiting apoptosis and promoting differentiation.
ANNALS OF HEMATOLOGY
(2023)
Review
Oncology
Cong Wang, Yamei Shen, Yuxia Zhang, Fahui Guo, Qian Li, Huahua Zhang, Xueping Han, Haitao Zhao, Zilong Yang
Summary: The co-occurrence of multiple primary cancers with hematological malignancies is uncommon, and acute promyelocytic leukemia (APL) with MPC is even rarer. In this article, we introduce the diagnosis and treatment of 2 cases of MPC complicated with APL in our hospital and review the relevant literature. Both patients were primary solid tumor patients and were treated with surgery and chemotherapy, and had stable disease (SD). However, more than 1 year after the primary tumor was diagnosed, clinical symptoms were found and APL was diagnosed. Both patients received standard remission-induction therapy, but unfortunately died in the short term due to hemorrhagic complications.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maedeh Mohebnasab, Peng Li, Bo Hong, Jennifer Dunlap, Elie Traer, Guang Fan, Richard D. Press, Stephen R. Moore, Wei Xie
Summary: Cytogenetically cryptic acute promyelocytic leukemia (APL) is a rare disease characterized by typical clinical and morphological features, but lacks detectable genetic translocation. Prompt diagnosis and treatment are crucial due to potential life-threatening complications. This study presents four cases of cryptic APL and reviews previous reports, highlighting the importance of parallel testing methods, especially reverse transcriptase polymerase chain reaction (RT-PCR), for accurate and effective diagnosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Shuang Fu, Mengqi Li, Hongtao Wang
Summary: This article describes a rare case of a 29-year-old man diagnosed with acute promyelocytic leukemia (APL) in 2019, who developed BCR-ABL1-positive acute lymphoblastic leukemia (ALL) 2 years later. The patient responded well to tyrosine kinase inhibitors and chemotherapy, achieving a molecular remission. While APL generally has a good prognosis, the prognosis of its secondary malignancies is uncertain. There are no effective measures to prevent the occurrence of secondary tumors. Increasing the frequency of laboratory testing, especially molecular biomarker monitoring, is crucial for diagnosing and treating secondary malignancies after achieving complete remission.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Oncology
Sabine Kayser, Shannon E. Conneely
Summary: This review summarizes the unique aspects of managing acute promyelocytic leukemia (APL) in very elderly and pediatric patients, focusing on treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), toxicities, and dose modifications. ATO/ATRA is the standard therapy for younger adult, non-high-risk APL patients, but early death remains a challenge, especially in older patients. Rapid diagnostics, immediate access to ATRA-based therapy, and supportive care are crucial. This review also discusses the management of toxicities and complications in APL patients.
Review
Oncology
Uday Kulkarni, Vikram Mathews
Summary: Treatment for acute promyelocytic leukemia has transformed from being the most malignant form of acute leukemia to one with excellent long term survival rates over the past three decades. Current treatment regimens for APL incorporate minimal chemotherapeutic drugs, with a potential future shift towards completely oral arsenic trioxide + ATRA regimen for low-intermediate risk cases. For high-risk cases, minimal anthracycline use with ATO + ATRA might become the standard of care soon. Promising non-chemotherapy drugs are being explored for high risk and relapsed cases, with a potential to translate to a complete oral chemotherapy free combination regimen in the future.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Laia Josa-Cullere, Katrina S. Madden, Thomas J. Cogswell, Thomas R. Jackson, Tom S. Carter, Douzi Zhang, Graham Trevitt, Stephen G. Davies, Paresh Vyas, Graham M. Wynne, Thomas A. Milne, Angela J. Russell
Summary: A novel compound, OXS007417, identified through a phenotypic high-throughput screen, shows promise in decreasing tumor volume in acute myeloid leukemia.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Xiang Zhang, Jiewen Sun, Wenjuan Yu, Jie Jin
Summary: Acute promyelocytic leukemia (APL) consists of typical APL and variant APL, with the latter showing distinct features and challenges in recognition, diagnosis, and treatment. Genetic studies have revealed a great heterogeneity in the genetics of variant APL, with different rearrangements other than RARA/RARB/RARG being able to drive the disease. Treatment for variant APL often involves combined chemotherapy instead of differentiation induction therapy.
BIOMARKER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Xibao Yu, Xin Liu, Xuan Liu, Shuang Jin, Mengjun Zhong, Dingrui Nie, Xiangbo Zeng, Xianfeng Wang, Jiaxiong Tan, Yangqiu Li, Chengwu Zeng
Summary: CASP1/GSDMD expression is lower in patients with acute promyelocytic leukemia (APL) and most other subtypes of primary de novo acute myeloid leukemia (AML), but is increased in all-trans-retinoic acid (ATRA)-treated APL cells; ATRA induces CASP1 expression via the IFN gamma/STAT1 pathway and triggers pyroptotic cell death and differentiation in APL cells, serving as a suppressor in APL progression.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Genetics & Heredity
Zeljko Antic, Stefan H. Lelieveld, Cedric G. van der Ham, Edwin Sonneveld, Peter M. Hoogerbrugge, Roland P. Kuiper
Summary: Investigating mutations in clusters separated in time may help understand mutational mechanisms and discover underlying causes.
Article
Hematology
Stephane de Botton, Pau Montesinos, Andre C. Schuh, Cristina Papayannidis, Paresh Vyas, Andrew H. Wei, Hans Ommen, Sergey Semochkin, Hee-Je Kim, Richard A. Larson, Jaime Koprivnikar, Olga Frankfurt, Felicitas Thol, Joerg Chromik, Jenny Byrne, Arnaud Pigneux, Xavier Thomas, Olga Salamero, Maria Belen Vidriales, Vadim Doronin, Hartmut Doehner, Amir T. Fathi, Eric Laille, Xin Yu, Maroof Hasan, Patricia Martin-Regueira, Courtney D. DiNardo
Summary: This study compared the efficacy of the oral IDH2 inhibitor enasidenib with conventional care regimens (CCR) in older patients with late-stage mutant-IDH2 AML. Enasidenib significantly improved event-free survival, time to treatment failure, overall response rate, hematologic improvement, and transfusion independence compared to CCR. However, there was no significant difference in overall survival, possibly due to early dropout and subsequent AML-directed therapies.
Article
Hematology
Misha C. Tran, Yasmin Hasan, Amy Wang, Kamil Yenice, Julien Partouche, Wendy Stock, Richard A. Larson, Satyajit Kosuri, James L. LaBelle, Justin Kline, Peter A. Riedell, Andrew S. Artz, Ralph Weichselbaum, Michael R. Bishop, Bulent Aydogan, Hongtao Liu
Summary: Relapse after allo-SCT is a common issue, and a second SCT can be considered for treatment. The study explored the feasibility of combining IM-TMI with fludarabine and melphalan for conditioning in patients undergoing a second or greater allo-SCT. The results showed that the combination therapy was feasible and achieved favorable outcomes.
Article
Hematology
Andrew J. Shih, Tomi Jun, Andrew D. Skol, Riyue Bao, Lei Huang, Sapana Vora, Megan E. McNerney, Eric A. Hungate, Michelle M. Le Beau, Richard A. Larson, Aaron Elliott, Hsiao-Mei Lu, Robert Huether, Felicia Hernandez, Friedrich Stolzel, James M. Allan, Kenan Onel
Summary: Some patients with therapy-related myeloid neoplasms (t-MN) may have unsuspected inherited cancer predisposition syndrome (CPS). A set of clinical criteria has been proposed to identify t-MN patients with high risk of CPS (HR-CPS). Among the identified HR-CPS patients, 37% had pathogenic or likely pathogenic variants, compared to 0% in the low-risk CPS patients. These simple clinical criteria help identify t-MN patients most likely to benefit from genetic testing for inherited CPS.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Jorge E. Cortes, Andreas Hochhaus, Naoto Takahashi, Richard A. Larson, Ghayas C. Issa, Felice Bombaci, Nicholas Ramscar, Sophie Ifrah, Timothy P. Hughes
Summary: Asciminib, a BCR-ABL1 inhibitor that works through the STAMP mechanism, has shown favorable efficacy and safety in patients with chronic myeloid leukemia in chronic phase. The ongoing ASC4FIRST trial aims to compare the effectiveness of Asciminib with investigator-selected TKIs in newly diagnosed patients with chronic myeloid leukemia.
Article
Integrative & Complementary Medicine
Nilanjana Basu, Manoj Garg, Chanderdeep Tandon, Bhudev Chandra Das, Simran Tandon
Summary: The study evaluated the anti-cancer potential of arsenic trioxide in hormone-dependent breast cancer. The results showed that arsenic trioxide could inhibit cell proliferation, induce apoptosis, and reduce cell migration in breast cancer cells. Further research is needed to elucidate the mechanism of action of arsenic trioxide in vivo.
Article
Hematology
Dorit Blickstein, Marina Izak, Talia Filipovich-Rimon, Osnat Garach-Jehoshua, Naomi Rahimi-Levene, Eilat Shinar, Ramzia Abu Hamad, Adina Bar-Chaim, Maya Koren-Michowitz
Summary: This study aimed to evaluate the prevalence of antiphospholipid antibodies (APLA) in convalescent plasma (CP) obtained from COVID-19 patients and assess the potential risk of thrombosis in transfused patients. The results showed that out of 122 CP samples, 7 samples (6%) tested positive for APLA. The low prevalence of APLA in CP donors reassured the safety of CP administration to patients with severe COVID-19.
Article
Chemistry, Multidisciplinary
Dolly Sharma, Mamta Singh, Jayadev Joshi, Manoj Garg, Vidhi Chaudhary, Daniel Blankenberg, Sudhir Chandna, Vinit Kumar, Reshma Rani
Summary: A series of new thiazole-based small molecules were designed using a computer simulation approach and showed strong inhibition of hLDHA. Molecular docking analysis revealed specific amino acids that interacted strongly with the designed compounds. The synthesized compounds demonstrated good hLDHA inhibitory activity and anticancer activity in multiple cancer cell lines, with compounds 8b, 8c, and 8l showing the highest inhibitory activity. These compounds also exhibited significant anticancer activity in liver cancer cells without noticeable toxicity in human cells, indicating their potential as therapeutic agents. In silico profiling confirmed the drug-likeness of the compounds and suggested their suitability for further development.
Article
Biochemistry & Molecular Biology
Sigal Avraham, Leonie Schuetz, Larissa Kaever, Andreas Dankers, Sapir Margalit, Yael Michaeli, Shahar Zirkin, Dmitry Torchinsky, Noa Gilat, Omer Bahr, Gil Nifker, Maya Koren-Michowitz, Elmar Weinhold, Yuval Ebenstein
Summary: The article presents a new high-throughput platform for multi-color epigenetic analysis, which allows simultaneous detection of methylation and demethylation signals. By utilizing an engineered methyltransferase enzyme and enzymatic glycosylation, the study achieves simultaneous measurement of 5-hydroxymethylcytosine and 5-methylcytosine. The findings demonstrate the potential of using a simple blood test for epigenetic evaluation in clinical samples, benefiting research and patient management.
Article
Biochemistry & Molecular Biology
Sunil Kumar, Iqra Ali, Faheem Abbas, Anurag Rana, Sadanand Pandey, Manoj Garg, Deepak Kumar
Summary: In this study, a library of 1843 benzimidazole-1,2,3-triazole hybrids was screened to identify potential epidermal growth factor receptor (EGFR) inhibitors for lung cancer treatment. The identified compounds showed stable interactions with EGFR and exhibited favorable drug-likeness properties and low toxicity. This research provides important insights into the development of potent and selective EGFR inhibitors for lung cancer treatment.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Oncology
Naval G. Daver, Paresh Vyas, Suman Kambhampati, Monzr M. Al Malki, Richard A. Larson, Adam S. Asch, Gabriel Mannis, Wanxing Chai-Ho, Tiffany N. Tanaka, Terrence J. Bradley, Deepa Jeyakumar, Eunice S. Wang, Kendra Sweet, Hagop M. Kantarjian, Guillermo Garcia-Manero, Rami Komrokji, Guan Xing, Giridharan Ramsingh, Camille Renard, Joshua F. Zeidner, David A. Sallman
Summary: Magrolimab combined with azacitidine showed promising efficacy and tolerability in patients with untreated AML ineligible for intensive chemotherapy, including those with TP53 mutations.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Samarth Kansara, Agrata Singh, Abhishesh Kumar Badal, Reshma Rani, Prakash Baligar, Manoj Garg, Amit Kumar Pandey
Summary: Altered energy metabolism is a key characteristic of tumorigenesis, and non-coding RNAs (ncRNAs) play a significant role in regulating glucose metabolism in human cancers. In this review, the aberrant expression of glucose metabolic pathways in breast cancer is outlined, and the potential applications of ncRNAs in regulating energy pathways, as well as their importance in prognosis, diagnosis, and future therapeutics for breast carcinoma, are discussed.
SEMINARS IN CANCER BIOLOGY
(2023)
Article
Hematology
Marta Verna, Marta Canesi, Valentino Conter, Lawrence Faulkner, Attilio Maria Rovelli, Daniela Silvestri, Ignazio Majolino, Andrea Biondi, Chra Nawfal Abdullah, Vian Faeq Mohammed
Summary: Thalassemia is a common and life-threatening disorder in children in regions prone to hemoglobinopathy, such as the Middle East. Hematopoietic stem cell transplantation (HSCT) is a highly effective and cost-effective treatment for thalassemia. A study in Iraqi Kurdistan demonstrated the successful establishment of an HSCT unit for both adults and children, achieving comparable results to international standards. The success of the program relied on meeting minimum requirements, international collaboration, and capacity-building efforts.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Hematology
Alexander E. Perl, Richard A. Larson, Nikolai A. Podoltsev, Stephen Strickland, Eunice S. Wang, Ehab Atallah, GaryJ. Schiller, Giovanni Martinelli, Andreas Neubauer, Jorge Sierra, Pau Montesinos, Christian Recher, Sung-Soo Yoon, Yoshinobu Maeda, Naoko Hosono, Masahiro Onozawa, Takayasu Kato, Hee-Je Kim, Nahla Hasabou, Rishita Nuthethi, Ramon Tiu, Mark J. Levis
Summary: The ADMIRAL trial investigated the efficacy of using the FLT3 inhibitor gilteritinib as maintenance therapy after hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory FLT3-mutated AML. The results showed that gilteritinib maintenance therapy improved survival rates and was well-tolerated in patients post-HSCT.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Hematology
Alessandro Cattoni, Giulia Capitoli, Sara Casagranda, Paola Corti, Marta Adavastro, Alessandro Molinaro, Filiberto Di Gennaro, Sonia Bonanomi, Andrea Biondi, Stefania Galimberti, Adriana Balduzzi
Summary: This retrospective study aimed to assess the prevalence, severity, risk factors, and management of iron overload (IOL) in pediatric patients who underwent hematopoietic stem cell transplantation (HSCT). The results showed that 73% of patients had some degree of IOL, with a higher severity observed in patients with malignant diseases. Pre-HSCT and maximum post-HSCT ferritin levels were statistically higher in patients with malignancies, and radiologic assessment confirmed a more severe degree of IOL in these patients.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Medicine, General & Internal
Srdan Verstovsek, Aaron T. Gerds, Alessandro M. Vannucchi, Haifa Kathrin Al-Ali, David Lavie, Andrew T. Kuykendall, Sebastian Grosicki, Alessandra Iurlo, Yeow Tee Goh, Mihaela C. Lazaroiu, Miklos Egyed, Maria Laura Fox, Donal McLornan, Andrew Perkins, Sung -Soo Yoon, Vikas Gupta, Jean -Jacques Kiladjian, Nikki Granacher, Sung-Eun Lee, Luminita Ocroteala, Francesco Passamonti, Claire N. Harrison, Barbara J. Klencke, Sunhee Ro, Rafe Donahue, Jun Kawashima, Ruben Mesa
Summary: This study aimed to compare the clinical effects of momelotinib and danazol in patients with intermediate or high-risk myelofibrosis. The results showed that momelotinib can significantly improve myelofibrosis-associated symptoms, anemia measures, and spleen response compared to danazol, with favorable safety.