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
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)
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
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
Oncology
Harinder Gill, Radha Raghupathy, Carmen Y. Y. Lee, Yammy Yung, Hiu-Tung Chu, Michael Y. Ni, Xiao Xiao, Francis P. Flores, Rita Yim, Paul Lee, Lynn Chin, Vivian W. K. Li, Lester Au, Wing-Yan Au, Edmond S. K. Ma, Diwakar Mohan, Cyrus Rustam Kumana, Yok-Lam Kwong
Summary: This study found that the incidence of acute promyelocytic leukaemia (APL) is increasing, and the use of oral arsenic trioxide (oral-ATO) in treatment has significantly improved patient survival rates.
Review
Cell Biology
Saghar Yousefnia
Summary: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia characterized by translocation between specific genes. Arsenic trioxide (ATO) is an important treatment agent for APL, inducing apoptosis, autophagy, differentiation, and inhibiting cell growth and angiogenesis. Understanding the effects of ATO on signaling pathways can lead to novel treatment strategies for leukemia and other cancer cells.
CELL BIOLOGY INTERNATIONAL
(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
Serena Rosati, Carmelo Gurnari, Massimo Breccia, Ida Carmosino, Emilia Scalzulli, Enrico Montefusco, Salvatore Perrone, Ombretta Annibali, Vincenza Martini, Giulio Trape, Gioia Colafigli, Malgorzata Trawinska, Clara Minotti, Giuseppe Cimino, Agostino Tafuri, Giuseppe Avvisati, Maurizio Martelli, Maria Teresa Voso, Roberto Latagliata
Summary: The study found that nearly half of older APL patients aged 70 and above received sub-optimal induction treatments, leading to dismal outcomes. This highlights the importance of adopting standard therapies instead of modified or reduced personalized approaches in the setting of frail older patients.
Article
Biochemistry & Molecular Biology
Xinping Huang, Yongfeng Yang, Dan Zhu, Yan Zhao, Min Wei, Ke Li, Hong-Hu Zhu, Xiaofeng Zheng
Summary: The research reveals that PRMT5 is highly expressed in APL patients and promotes APL by interacting with PML-RAR alpha. Inhibition of PRMT5 effectively blocks the growth of APL cells, and combined use with As2O3 shows promise as a therapeutic strategy against APL.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Medicine, Research & Experimental
Wenran Dan, Liang Zhong, Lihua Yu, Ling Xiong, Jian Li, Jiao Ye, Xu Luo, Chen Liu, Xuan Chu, Beizhong Liu
Summary: This study investigates the role of Skp2 and JunB in the progression of acute promyelocytic leukemia (APL) and the related mechanisms. The results show that elevated Skp2 expression promotes APL progression by decreasing the expression of lncRNA HOTAIRM1 and inhibiting GSK3β, leading to autophagy inhibition and the suppression of PML-RARα ubiquitylation and degradation. This represses JunB transcriptional activation through the PU.1/PML-RARα transcriptional complex, blocking cell differentiation. Inhibition of Skp2 induces JunB expression and contributes to the eradication of APL by accelerating the degradation of PML-RARα. The expressions of Skp2 and JunB are negatively correlated in mice subcutaneous leukemia xenograft tumors.
Article
Hematology
Yun Tan, Xiaoling Wang, Huan Song, Yi Zhang, Rongsheng Zhang, Shufen Li, Wen Jin, Saijuan Chen, Hai Fang, Zhu Chen, Kankan Wang
Summary: The activation function of PML/RAR alpha through recruiting P300 and HDAC1 and forming super-enhancers, and its synergistic effects with all-trans retinoic acid and arsenic trioxide in controlling super-enhancer-associated PML/RAR alpha-regulated targets in APL cells are highlighted. The study demonstrated the necessity of the PML/RAR alpha-activated target gene GFI1 for maintaining APL cells and the interplay between GFI1 and PML/RAR alpha in coregulating target genes on chromatin. Genomic insight into the dual role of fusion transcription factors in transcriptional deregulation to drive leukemia development is provided, emphasizing the importance of globally dissecting regulatory circuits.
Review
Oncology
Sunil Girish Iyer, Laila Elias, Michele Stanchina, Justin Watts
Summary: The transformation of acute promyelocytic leukemia (APL) from a fatal disease to a highly curable cancer is a remarkable success in oncology. Targeted therapies have played a significant role in achieving high cure rates without the need for chemotherapy. This review discusses the current treatment paradigm for APL in 2023, emphasizes the importance of prompt initiation of treatment, and explores novel agents and future directions for improving cure rates and quality of life for APL patients.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell Biology
Diego A. Pereira-Martins, Isabel Weinhauser, Juan Luiz Coelho-Silva, Pedro L. Franca-Neto, Luciana Y. Almeida, Thiago M. Bianco, Cleide L. Silva, Rafael F. Franca, Fabiola Traina, Eduardo M. Rego, Jan Jacob Schuringa, Antonio R. Lucena-Araujo
Summary: The study revealed the critical role of MLL5 in APL, regulating mtROS, epigenetic modifiers, and ATRA-induced granulocytic differentiation, which enhances cell proliferation and drug resistance.
CELL DEATH & DISEASE
(2021)
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
Matteo Molica, Carla Mazzone, Tiziana Ottone, Pasquale Niscola, Elisabetta Abruzzese, Stefano Fratoni, Maria Teresa Voso, Paolo de Fabritiis
Summary: Relapses of acute promyelocytic leukemia (APL) beyond 7 years from the first molecular remission are rare, and it is unclear whether these relapses represent a therapy-related leukemia or a delayed relapse of the original leukemic clone. The increase in extra-medullary relapses (ER) in the era of all-trans retinoic acid (ATRA) therapy suggests a potential correlation between ATRA therapy and ER, and the optimal post-remission approach for late relapse patients remains to be established.
FRONTIERS IN ONCOLOGY
(2021)
