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1.
Acute promyelocytic leukemia with myelofibrosis: A case report and literature review.
Xiao, M, Qin, L, Niu, X, Zhou, P, Niu, J, Wei, S, Li, D, Dou, L, Zhang, W, Zhang, L, et al
Medicine. 2021;(13):e24567
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Abstract
RATIONALE Acute promyelocytic leukemia (APL) with myelofibrosis (MF) is rare, and only 14 cases have been reported in the literature to date. PATIENT CONCERNS A 42-year-old woman was admitted to the hospital with easy bruising and excessive bleeding. With the remission of the primary disease during treatment, the degree of fibrosis did not decrease, but worsened progressively. DIAGNOSIS The woman was diagnosed with acute promyelocytic leukemia with secondary myelofibrosis. INTERVENTIONS All-trans retinoic acid (ATRA) was discontinued after 6 months of complete remission of APL. Arsenic trioxide (ATO) was discontinued because of supraventricular tachycardia 9 months after complete remission of APL. OUTCOMES After withdrawal of ATRA for 2 months, the degree of fibrosis was significantly alleviated, and after withdrawal of ATRA for 8 months and ATO for 5 months, bone marrow biopsy showed no reticular fiber deposition. LESSONS In this case report and review of an additional 14 cases of APL with MF, we highlighted the importance of the degree of MF to be evaluated by bone marrow biopsy at the time of bone marrow aspiration when APL is suspected. If MF is present, the type of MF should be determined in a timely manner, and appropriate intervention measures should be taken accordingly.
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2.
Post-translational modification of retinoic acid receptor alpha and its roles in tumor cell differentiation.
Xu, A, Zhang, N, Cao, J, Zhu, H, Yang, B, He, Q, Shao, X, Ying, M
Biochemical pharmacology. 2020;:113696
Abstract
Retinoic acid (RA) is a well-known differentiation inducer that exerts its effects by binding to nuclear RA receptors. Retinoic acid receptor α (RARα), as an important nuclear RA receptor, is activated upon RA binding and facilitates the transcription of target genes related to differentiation, which ultimately initiates cell differentiation. Previous studies have found that the transcriptional activity of RARα is regulated by various post-translational modifications, which influence its DNA binding efficiency, transactivation ability and even lead to degradation. Post-translational modifications of RARα, as a consequence, play an important role in the RA-induced differentiation process. Therefore, in this review, we focus on recent advances in the understanding of how these modifications affect the activity of RARα as well as strategies to increase the differentiation effect of RA treatment in cancer cells based on RARα modifications, which may promote the development of novel effective differentiation therapies for cancer treatment.
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3.
Acute myeloid leukemia during pregnancy: a single institutional experience with 17 patients and literature review.
Li, YW, Xu, YF, Hu, W, Qian, SX, Chen, C
International journal of hematology. 2020;(4):487-495
Abstract
Management of acute myeloid leukemia during pregnancy (P-AML) is a challenging endeavor with limited evidence-based information available. To truly achieve the goal of improving P-AML patients, additional evidence-based research is necessary. We retrospectively reviewed cases of 17 patients diagnosed with P-AML, including seven for acute promyelocytic leukemia (APL) from January 2012 to June 2019. Among the non-APL, 90% patients (9/10) ended pregnancy prior to induction chemotherapy. The median intervals between diagnosis and start of chemotherapy were 5 days (range 1-14 days). Four patients elected to delay chemotherapy by more than one week. Of the seven APL patients, six received all-trans retinoic acid (ATRA) before the diagnostic molecular results. Five patients underwent cesarean sections (CS) and all newborns were alive (four preterm and one full-term deliveries). Overall, approximately 94% of the patients (16/17) are currently alive in remission. To treat P-AML patients in a safer manner, balancing the risk of progressing to advanced disease and proceeding with pregnancy is required. We consider a slight delay (less than 14 days) in the termination of pregnancy may not differ the prognosis to patients with non-APL. For APL, patients will benefit from prompt administration of ATRA for highly suspected cases.
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4.
Fetal Alcohol Spectrum Disorder: Embryogenesis Under Reduced Retinoic Acid Signaling Conditions.
Fainsod, A, Bendelac-Kapon, L, Shabtai, Y
Sub-cellular biochemistry. 2020;:197-225
Abstract
Fetal Alcohol Spectrum Disorder (FASD) is a complex set of developmental malformations, neurobehavioral anomalies and mental disabilities induced by exposing human embryos to alcohol during fetal development. Several experimental models and a series of developmental and biochemical approaches have established a strong link between FASD and reduced retinoic acid (RA) signaling. RA signaling is involved in the regulation of numerous developmental decisions from patterning of the anterior-posterior axis, starting at gastrulation, to the differentiation of specific cell types within developing organs, to adult tissue homeostasis. Being such an important regulatory signal during embryonic development, mutations or environmental perturbations that affect the level, timing or location of the RA signal can induce multiple and severe developmental malformations. The evidence connecting human syndromes to reduced RA signaling is presented here and the resulting phenotypes are compared to FASD. Available data suggest that competition between ethanol clearance and RA biosynthesis is a major etiological component in FASD.
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5.
Cellular Retinoic-Acid Binding Protein 2 in Solid Tumor.
Jiao, X, Liu, R, Huang, J, Lu, L, Li, Z, Xu, L, Li, E
Current protein & peptide science. 2020;(5):507-516
Abstract
The retinoic acid (RA) signaling pathway is crucial for many biological processes. The RA transporter, Cellular Retinoic-Acid Binding Protein 2 (CRABP2), is abnormally expressed in various tumor types. CRABP2 presents significant effects on tumorous behaviors and functions, including cell proliferation, apoptosis, invasion, migration, metastasis, and angiogenesis. The tumorigenesis mechanism of CRABP2, as both suppressor and promotor, is complicated, therefore, there remains the need for further investigation. Elucidating the regulating mechanisms in a specific stage of the tumor could facilitate CRABP2 to be a biomarker in cancer diagnosis and prognosis. Besides, clarifying the pathways of CRABP2 in cancer development will contribute to the gene-targeted therapy. In this review, we summarized the expression, distribution, and mechanism of CRABP2 in solid tumors. Illuminating the CRABP2 signaling pathway may benefit understanding the retinoid signaling pathway, providing a useful biomarker for future clinical trials.
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6.
The role of lamin A/C in mesenchymal stem cell differentiation.
Zhang, B, Yang, Y, Keyimu, R, Hao, J, Zhao, Z, Ye, R
Journal of physiology and biochemistry. 2019;(1):11-18
Abstract
Lamin A/C is the major architectural protein of cell nucleus in charge of the nuclear mechanosensing. By integrating extracellular mechanical and biochemical signals, lamin A/C regulates multiple intracellular events including mesenchymal stem cell (MSC) fate determination. Herein, we review the recent findings about the effects and mechanisms of lamin A/C in governing MSC lineage commitment, with a special focus on osteogenesis and adipogenesis. Better understanding of MSC differentiation regulated by lamin A/C could provide insights into pathogenesis of age-related osteoporosis.
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7.
Acute Promyelocytic Leukemia and HIV: Case Reports and a Review of the Literature.
Kunitomi, A, Hasegawa, Y, Lmamura, J, Yokomaku, Y, Tokunaga, T, Miyata, Y, Iida, H, Nagai, H
Internal medicine (Tokyo, Japan). 2019;(16):2387-2391
Abstract
Acute promyelocytic leukemia (APL) in human immunodeficiency virus (HIV)-infected individuals is very rare. There is currently no consensus regarding the use of anti-cancer drugs with highly active anti-retroviral therapy (ART) in these patients due to their small number. We herein report two cases of APL with HIV-infected patients. Both cases received all-trans-retinoic acid-containing chemotherapies and achieved complete remission. ART was continued throughout the treatment course. The clinical course of these cases suggests that it is preferable to perform standard chemotherapy for APL with ART if patients have an adequate performance status.
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8.
Retinoic Acid and the Gut Microbiota in Alzheimer's Disease: Fighting Back-to-Back?
Endres, K
Current Alzheimer research. 2019;(5):405-417
Abstract
BACKGROUND There is growing evidence that the gut microbiota may play an important role in neurodegenerative diseases such as Alzheimer's disease. However, how these commensals influence disease risk and progression still has to be deciphered. OBJECTIVE The objective of this review was to summarize current knowledge on the interplay between gut microbiota and retinoic acid. The latter one represents one of the important micronutrients, which have been correlated to Alzheimer's disease and are used in initial therapeutic intervention studies. METHODS A selective overview of the literature is given with the focus on the function of retinoic acid in the healthy and diseased brain, its metabolism in the gut, and the potential influence that the bioactive ligand may have on microbiota, gut physiology and, Alzheimer's disease. RESULTS Retinoic acid can influence neuronal functionality by means of plasticity but also by neurogenesis and modulating proteostasis. Impaired retinoid-signaling, therefore, might contribute to the development of diseases in the brain. Despite its rather direct impact, retinoic acid also influences other organ systems such as gut by regulating the residing immune cells but also factors such as permeability or commensal microbiota. These in turn can also interfere with retinoid-metabolism and via the gutbrain- axis furthermore with Alzheimer's disease pathology within the brain. CONCLUSION Potentially, it is yet too early to conclude from the few reports on changed microbiota in Alzheimer's disease to a dysfunctional role in retinoid-signaling. However, there are several routes how microbial commensals might affect and might be affected by vitamin A and its derivatives.
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9.
[Acute promyelocytic leukemia: state-of-the-art management].
Asou, N
[Rinsho ketsueki] The Japanese journal of clinical hematology. 2018;(6):725-734
Abstract
Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML) -retinoic acid receptor (RAR) α fusion protein generated by the chromosomal translocation t (15;17) which affects both nuclear receptor signaling and PML nuclear body (NB) assembly. The advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as molecular targeted therapies directed against PML-RARα has been a major breakthrough in APL treatment. ATRA and ATO target RARα and PML, respectively, and elicit PML-RARα degradation, leading to the reformation of normal NBs and cell differentiation. In several multicenter trials, more than 90% of newly diagnosed APL patients treated with ATRA and chemotherapy achieved complete remission, of whom 20%-30% subsequently relapsed; the overall survival was approximately 80% in these studies. However, several major clinical problems continue to account for treatment failure including early death due to hemorrhage, infection during consolidation, disease relapse, and secondary malignancies. These issues are associated mainly with anticancer agents used in combination with ATRA. Combination therapy using ATRA and ATO is the current standard therapy for untreated patients with APL in Western countries. The current problems in patients with APL treated with ATRA and ATO are APL differentiation syndrome and high risk of relapse in patients with an initial leukocyte count of more than 10×109/l.
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10.
[Acute Promyelocytic Leukemia: New treatment strategies with ATRA and ATO - AML-BFM-Recommendations].
Creutzig, U, Dworzak, M, von Neuhoff, N, Rasche, M, Reinhardt, D
Klinische Padiatrie. 2018;(6):299-304
Abstract
The treatment of acute promyelocytic leukemia (APL) has changed significantly in recent years. Today, APL patients with standard risk (also known as low risk) can be treated chemotherapy-free only with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). For high-risk patients, induction chemotherapy should be added. The curative results are good and comparable to those achieved in the past with chemotherapy plus ATRA. However, toxicities, especially infectious complications, are reduced. The main risk remains early lethal bleeding. Timely diagnosis and early ATRA treatment can reduce this risk. This review presents and discusses current treatment strategies and recommendations for APL in children.