Article
Medicine, Research & Experimental
Tingyuan Yang, Xiayu Shi, Shiliang Li, Zhenjiang Zhao, Junyi Wang, Panpan Yu, Honglin Li, Rui Wang, Zhuo Chen
Summary: In this study, researchers discovered that inhibition of dihydroorotate dehydrogenase (DHODH) overcame resistance to all-trans retinoic acid (ATRA) in high-risk acute promyelocytic leukemia (APL) patients. A potent DHODH inhibitor, 416, was found to effectively inhibit APL in cells and model mice. Additionally, 416 overcame ATRA resistance by inducing apoptosis and differentiation, and maintained its down-regulation effect on Bcl-2 and c-Myc in APL cells.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Medicine, General & Internal
Bryan C. Hambley, Ciprian Tomuleasa, Gabriel Ghiaur
Summary: APL is characterized by a distinct coagulopathy, leading to frequent complications such as hemorrhage and thrombosis. Despite improvements in treatments and long-term survival rates, hemorrhagic and thrombotic complications remain the most common causes of death and morbidity in APL patients. Enhanced understanding of the coagulation mechanisms associated with APL may result in therapeutic interventions to reduce the risk of hemorrhage and thrombosis.
FRONTIERS IN MEDICINE
(2021)
Article
Oncology
Junmei Zhao, Wentao Wang, Li Yan, Xi Chen, Wen Li, Wanying Li, Tingting Chen, Lunhua Chen
Summary: Rearrangement of the retinoic acid receptor gamma (RARG) gene is a common occurrence in acute myeloid leukemia (AML) patients, resembling classical acute promyelocytic leukemia (APL) patients. However, they do not carry the promyelocytic leukemia (PML)-RARA fusion gene. These APL-like AML patients are typically resistant to all-trans retinoic acid (ATRA) and currently have no effective treatment options. This study identified a rare cleavage and polyadenylation-specific factor 6 (CPSF6)-RARG fusion gene in an AML case resembling APL. The patient showed insensitivity to ATRA and ATO but responded well to homoharringtonine and cytarabine.
FRONTIERS IN ONCOLOGY
(2022)
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
Luciana Yamamoto de Almeida, Diego A. Pereira-Martins, Isabel Weinhaeuser, Cesar Ortiz, Larissa A. Candido, Ana Paula Lange, Nayara F. De Abreu, Silvia E. S. Mendonza, Virginia M. de Deus Wagatsuma, Mariane C. Do Nascimento, Helder H. Paiva, Raquel M. Alves-Paiva, Camila C. O. M. Bonaldo, Daniele C. Nascimento, Jose C. Alves-Filho, Priscila S. Scheucher, Ana Silvia G. Lima, Jan Jacob Schuringa, Emanuele Ammantuna, Tiziana Ottone, Nelida I. Noguera, Cleide L. Araujo, Eduardo M. Rego
Summary: This study revealed that the EGFR pathway is active in APL patients, and the use of EGFR inhibitors can promote differentiation of APL cells, providing a potential strategy to alleviate resistance to ATRA and ATO.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Hong-Hu Zhu, Ya-Fang Ma, Kang Yu, Gui-Fang Ouyang, Wen-Da Luo, Ren-Zhi Pei, Wei-Qun Xu, Hui-Xian Hu, Shu-Ping Mo, Xiao-Hua Xu, Jian-Ping Lan, Jian-Ping Shen, Li-Hong Shou, Shen-Xian Qian, Wei-Ying Feng, Pu Zhao, Jin-Hong Jiang, Bei-Li Hu, Jin Zhang, Su-Ying Qian, Gong-Qiang Wu, Wen-Ping Wu, Lei Qiu, Lin-Jie Li, Xiang-Hua Lang, Sai Chen, Li-Li Chen, Jun-Bin Guo, Li-Hong Cao, Hui-Fang Jiang, Yong-Ming Xia, Jing Le, Jian-Zhi Zhao, Jian Huang, Yue-Feng Zhang, Ya-Li Lv, Jing-Sheng Hua, Yong-Wei Hong, Cui-Ping Zheng, Ju-Xiang Wang, Bin-Fei Hu, Xiao-Hui Chen, Li-Ming Zhang, Shi Tao, Bing-Shou Xie, Yue-Min Kuang, Wen-Ji Luo, Ping Su, Jun Guo, Xiao Wu, Wei Jiang, Hui-Qi Zhang, Yun Zhang, Chun-Mei Chen, Xiao-Feng Xu, Yan Guo, Jin-Ming Tu, Shao Hu, Xiao-Yan Yan, Chen Yao, Yin-Jun Lou, Jie Jin
Summary: This population-based study in Zhejiang Province, China, found that ATRA and arsenic as front-line treatment are widely used and have low early death rate and high survival rate in real-world conditions. These results mimic those from clinical trials, supporting the broader application of APL guidelines in the future.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Mingyan Jiang, Jinrong Li, Jianrong Wu, Yiping Zhu, Ju Gao
Summary: This case report describes a patient with TBL1XR1-RARB positive APL, who had an early onset and no apparent bleeding tendency or coagulation dysfunction. The patient was resistant to ATRA and ATO, but had a good response to conventional chemotherapy for AML.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bo Dai, Feng Wang, Ying Wang, Jiayan Zhu, Yunxuan Li, Tingting Zhang, Luyao Zhao, Lining Wang, Wenhui Gao, Junmin Li, Honghu Zhu, Ke Li, Jiong Hu
Summary: Acute promyelocytic leukemia (APL) is driven by PML-RAR alpha oncoprotein, which is suppressed by HDAC3 inhibition to reduce the expression of PML-RAR alpha and induce differentiation, apoptosis, and decreased self-renewal of APL cells. HDAC3 deacetylates PML-RAR alpha, reducing its SUMOylation and subsequent ubiquitylation. Inhibiting HDAC3 with drugs or genetic methods shows promise as a strategy to treat relapsed/refractory APL.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Oncology
Rory Shein, Nomusa Mashigo, Cecile E. du Toit, Jenna Oosthuizen, Matthew D. Seftel, Vernon J. Louw, Estelle Verburgh
Summary: A retrospective study on APL patients treated in Cape Town, South Africa from 1998 to 2019 found that outcomes of patients at the center are similar to those in developed countries. Despite challenges in the public healthcare system of a developing country, the survival rates of APL patients are promising.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2021)
Article
Oncology
Marcus J. Geer, Charles E. Foucar, Sumana Devata, Lydia Benitez, Anthony J. Perissinotti, Bernard L. Marini, Dale Bixby
Summary: Less than one-third of hospitals in the United States had ATRA in stock, and hospitals treating patients with APL were more likely to have ATRA available compared to referring centers. These findings suggest a need to ensure immediate availability of ATRA for patients suspected of having APL.
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
(2021)
Article
Pharmacology & Pharmacy
Maria Franza, Jacopo Albanesi, Benedetta Mancini, Rosa Pennisi, Stefano Leone, Filippo Acconcia, Fabrizio Bianchi, Alessandra di Masi
Summary: This study investigates the effects of MK-8776, a specific inhibitor of CHK1, on ATRA-resistant APL cells. Treatment with MK-8776 induces degradation of PML-RARa, increased expression of CD11b, and differentiation of APL cells. Combining MK-8776 with ATO shows a synergistic effect. This study suggests that MK-8776 could be a potential therapeutic option for APL patients resistant to standard ATRA/ATO therapy.
BIOCHEMICAL PHARMACOLOGY
(2023)
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
Hematology
Albin Osterroos, Tania Maia, Anna Eriksson, Martin Jadersten, Vladimir Lazarevic, Lovisa Wennstrom, Petar Antunovic, Jorg Cammenga, Stefan Deneberg, Fryderyk Lorenz, Lars Mollgard, Bertil Uggla, Emma Olander, Eliana Aguiar, Fernanda Trigo, Martin Hoglund, Gunnar Juliusson, Soren Lehmann
Summary: The study aimed to develop a score that predicts the risk of early death (ED) in patients with acute promyelocytic leukemia. By analyzing patient registries from Sweden and Portugal, white blood cell count, platelet count, and age were identified as the most significant variables for predicting ED. The score successfully differentiated patients at different risk levels and was able to predict ED risk even at sub-normal/normal white blood cell counts.
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
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)
