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Promyelocytic leukemia

A P Jillella, V K Kota
Acute promyelocytic leukemia (APL) is a hyper-acute illness and presents with profound cytopenias in most patients and disseminated intravascular coagulation (DIC). Excellent treatment options are now available with drugs such as all-trans retinoic acid (ATRA), arsenic trioxide (ATO), anthracyclines and cytarabine. The outcome in APL has improved tremendously in the last 50years due to better understanding of the disease, development of effective targeted agents and improvement in supportive care. Carefully selected groups of patients treated in large multi-center trials on a protocol and in experienced centers have shown survival rates in excess of 85%...
September 18, 2017: Blood Reviews
Yannan Jia, Chengwen Li, Jiawei Zhao, Yang Song, Juan Wang, Yingchang Mi
Some chromosomal aberrations emerging in the course of treatment are probably not related to disease progression, but attribute to the germline alteration. Therefore, the dynamic genetic tests should be performed during the whole treatment process, which is significantly essential for efficacy evaluation and treatment decision- making.
October 2017: Clinical Case Reports
Shinya Okubo, Takuhiro Uto, Aya Goto, Hiroyuki Tanaka, Tsuyoshi Nishioku, Katsushi Yamada, Yukihiro Shoyama
Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR treatment in HL-60 human promyelocytic leukemia cells...
2017: American Journal of Chinese Medicine
Anna M Schläfli, Pauline Isakson, E Garattini, Anne Simonsen, Mario P Tschan
Acute myeloid leukemia (AML) is a malignancy of myeloid progenitor cells that are blocked in differentiation. Acute promyelocytic leukemia (APL) is a rare form of AML, which generally presents with a t(15;17) translocation causing expression of the fusion protein PML-RARA. Pharmacological doses of all-trans retinoic acid (ATRA) induce granulocytic differentiation of APL cells leading to cure rates of >80% if combined with conventional chemotherapy. Autophagy is a lysosomal degradation pathway for the removal of cytoplasmic content and recycling of macromolecules...
October 11, 2017: Scientific Reports
Yeung-Hyen Kim, Ajay Kumar, Cheong-Hee Chang, Kalyani Pyaram
Reactive oxygen species (ROS) are byproducts of aerobic metabolism and contribute to both physiological and pathological conditions as second messengers. ROS are essential for activation of T cells, but how ROS influence NKT cells is unknown. In the present study, we investigated the role of ROS in NKT cell function. We found that NKT cells, but not CD4 or CD8 T cells, have dramatically high ROS in the spleen and liver of mice but not in the thymus or adipose tissues. Accordingly, ROS-high NKT cells exhibited increased susceptibility and apoptotic cell death with oxidative stress...
October 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Céline Bouvy, Adeline Wannez, Julie Laloy, Christian Chatelain, Jean-Michel Dogné
The treatment of acute leukemia is still challenging due in part to the development of resistance and relapse. This chemotherapeutics resistance is established by clonal selection of resistant variants of the cancer cells. Recently, a horizontal transfer of chemo-resistance among cancer cells via extracellular vesicles (EVs) has been suggested. The aim of this research was to investigate the role of EVs in chemo-resistance in acute myeloid leukemia. For this purpose, the sensitive strain of the promyelocytic leukemia HL60 cell line was studied along with its multi-resistant strain, HL60/AR that overexpresses the multidrug resistance protein 1 (MRP-1)...
September 25, 2017: Leukemia Research
Junmin Zhang, Yaping Liu, Danfeng Shi, Guodong Hu, Baoxin Zhang, Xinming Li, Ruijuan Liu, Xiao Han, Xiaojun Yao, Jianguo Fang
Mammalian thioredoxin reductase (TrxR) enzymes play a crucial role in regulating multiple redox-based signaling pathways and have attracted increasing attention as promising anticancer drug targets. We report here the synthesis of a panel of naphthazarin derivatives and discovery of 2-methyl-5,8-dihydroxy-1,4-naphthoquinone (3, 2-methylnaphthazarin) as a potent cytotoxic agent with a submicromolar half maximal inhibitory concentration to the human promyelocytic leukemia HL-60 cells. Mechanism studies reveal that the compound selectively inhibits TrxR to induce oxidative stress-mediated apoptosis of HL-60 cells...
September 19, 2017: European Journal of Medicinal Chemistry
K Rahman, R Gupta, M K Singh, M K Sarkar, A Gupta, S Nityanand
INTRODUCTION: The genetic testing to confirm or rule out an acute promyelocytic leukemia (APL) typically takes a minimum of 24-72 hours. Flow cytometric immunophenotyping (FCI) on the other hand provides rapid and objective information to differentiate APL from non-APL. METHODS: FCI features, with single-tube 8-color combination using CD45, CD34, HAL-DR, CD11b, CD13, CD33, and CD117 and CD64, were compared for the 30 consecutive APL and 30 non-APL acute myeloid leukemia (AML) cases which morphologically mimicked an APL...
October 6, 2017: International Journal of Laboratory Hematology
Maria Jamalpour, Xiujuan Li, Lucia Cavelier, Karin Gustafsson, Gustavo Mostoslavsky, Martin Höglund, Michael Welsh
The mouse Shb gene coding for the Src Homology 2-domain containing adapter protein B has recently been placed in context of BCRABL1-induced myeloid leukemia in mice and the current study was performed in order to relate SHB to human acute myeloid leukemia (AML). Publicly available AML databases were mined for SHB gene expression and patient survival. SHB gene expression was determined in the Uppsala cohort of AML patients by qPCR. Cell proliferation was determined after SHB gene knockdown in leukemic cell lines...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Christine Chomienne
No abstract text is available yet for this article.
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Nobuhiko Emi
Acute promyelocytic leukemia (APL) is defined by its characteristic morphology (AML FAB M3/M3v), specific chromosomal translocation t (15;17), and molecular correlates (PML/RARα). Treatment with all-trans retinoic acid (ATRA) combined with chemotherapy has a high cure rate. Clinical trials with arsenic trioxide (ATO) confirmed the efficacy of ATO for patients with relapsed APL. Recently, treatment with ATRA and ATO has been shown to result in high CR rates for the majority of patients with newly diagnosed APL...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Magali Humbert, Elena A Federzoni, Mario P Tschan
We have previously demonstrated that the death-associated protein kinase 2 (DAPK2) expression is significantly reduced in acute myeloid leukemia (AML), particularly in acute promyelocytic leukemia (APL) blast cells. In this study, we aimed at further understanding DAPK2 function and regulation during arsenic trioxide (ATO) cytotoxic or all-trans retinoic acid (ATRA) differentiation therapy in APL cells. We found that the p53 family member transactivation domain-p73 isoform (TAp73) binds to and activates the DAPK2 promoter, whereas the dominant-negative ΔNp73 isoform inhibits DAPK2 transcription...
October 4, 2017: Journal of Leukocyte Biology
Kendra D Nyberg, Kenneth H Hu, Sara H Kleinman, Damir B Khismatullin, Manish J Butte, Amy C Rowat
Advances in methods that determine cell mechanical phenotype, or mechanotype, have demonstrated the utility of biophysical markers in clinical and research applications ranging from cancer diagnosis to stem cell enrichment. Here, we introduce quantitative deformability cytometry (q-DC), a method for rapid, calibrated, single-cell mechanotyping. We track changes in cell shape as cells deform into microfluidic constrictions, and we calibrate the mechanical stresses using gel beads. We observe that time-dependent strain follows power-law rheology, enabling single-cell measurements of apparent elastic modulus, Ea, and power-law exponent, β...
October 3, 2017: Biophysical Journal
Yun Yu, Juqiang Lin, Duo Lin, Shangyuan Feng, Weiwei Chen, Zufang Huang, Hao Huang, Rong Chen
In this study, an electroporation-based surface-enhanced Raman scattering (SERS) technique was employed to differentiate the human myeloid leukemia cells from the normal human bone marrow mononuclear cells with the aim to develop a fast and label-free method for leukemia cell screening. The Ag nanoparticles were delivered into living cells by electroporation, and then high quality SERS spectra were successfully obtained from 60 acute promyelocytic leukemia cells (HL60 cell line), 60 chronic myelogenous leukemia cells (K562 cell line) and 60 normal human bone marrow mononuclear cells (BMC)...
September 1, 2017: Biomedical Optics Express
Jacqueline J Stevens, Barbara Graham, Erika Dugo, Bezawit Berhaneselassie-Sumner, Kenneth Ndebele, Paul B Tchounwou
BACKGROUND: Arsenic trioxide (ATO) is highly effective in the treatment of patients with acute promyelocytic leukemia (APL). It is a chemotherapeutic agent that has been shown to induce apoptosis in several tumor cell lines. However, research into its effects on colon carcinoma cells is still very limited. We previously reported that ATO is cytotoxic and causes DNA damage in HT-29 human colorectal adenocarcinoma cells. In the present study, we further evaluated its effect on oxidative stress (OS), and examined its apoptotic mechanisms of action on HT-29 cells...
January 2017: Journal of Cancer Science & Therapy
Tanmay Sahai, Kelly Henrichs, Majed Refaai, Joanna M Heal, Scott A Kirkley, Amy E Schmidt, Jason H Mendler, Debra Masel, Jane Liesveld, Christopher Aquina, Neil Blumberg
BACKGROUND: Despite dramatically improved long term outcomes seen with all-trans retinoic acid therapy, and now arsenic trioxide, in acute promyelocytic leukemia (APL), early mortality remains a substantial challenge. Recent data from a single center study and the Surveillance, Epidemiology and End Results (SEER) registry report 30day mortality rates of 26% (n=18 of 70) and 17% (n=238 of 1400), respectively. Early deaths are predominately due to hemorrhage. Patients with APL invariably have abnormal laboratory hemostasis tests...
September 23, 2017: Leukemia Research
Chen Chen, Hui-Jie Wang, Fu-Rong Liu, Yin Wang, Sheng-Jun Mao, Hui Jin
In this study, the tanshinone ⅡA loaded albumin nanoparticles were prepared by high pressure homogenization method. The formulation was optimized by central composite design-response surface method (CCD-RSM), with the particle size, encapsulation efficiency, and drug loading as indexes to investigate their in vitro anti-tumor effect. The results showed that the prepared nanoparticles had uniformly spherical morphology and uniform particle size distribution. The average particle size, encapsulation efficiency and drug loading of nanoparticles were about (175...
February 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Raquel Frenedoso da Silva, Cibele Dos Santos Borges, Celina de Almeida Lamas, Valéria Helena Alves Cagnon, Wilma de Grava Kempinas
The acute promyelocytic leukemia (APL) is a rare disease, affecting 0.1/100,000 individuals globally. Despite significant advances in APL therapy, some patients still experience relapsed disease. Currently, arsenic trioxide (As2O3) was found to be effective in relapsed APL treatment and considered as standard treatment for these cases. However, it has been shown that exposure to As2O3 may exert adverse effects on the male reproductive system since this substance might also induce apoptosis of other important cell types including stem cells...
September 28, 2017: Journal of Toxicology and Environmental Health. Part A
N Zhao, H Wei, Y Wang, D Lin, C L Zhou, B C Liu, K Q Liu, G J Zhang, S N Wei, B F Gong, X Y Gong, W Li, Y Li, Y T Liu, S W Qiu, R X Gu, Y C Mi, J X Wang
Objective: To probe the potential utility of Wilms tumor 1 (WT1) as a marker of minimal residual disease (MRD) in acute myeloid leukemia (AML) to estimate the relapse-predicting cut-off value. Methods: Quantitative assessment of bone marrow WT1 mRNA level was preformed using real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) assay. The expression levels of WT1 dynamically measured with RQ-RT-PCR were retrospectively analyzed in 121 AML cases (not including acute promyelocytic leukemia) achieving complete remission (CR) after induction therapy followed by consolidation therapy...
August 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
H Youn, H-K Lee, H-R Sohn, U-H Park, E-J Kim, B Youn, S-J Um
Retinoic acid (RA) has broad clinical applications for the treatment of various cancers, particularly acute promyelocytic leukemia. However, RA-based therapy is limited by relapse in patients associated with RA resistance, the mechanism of which is poorly understood. Here, we suggest a new molecular mechanism of RA resistance by a repressor, named RA resistance factor (RaRF). RaRF suppressed transcriptional activity of the RA receptor (RAR) by directly interacting with and sequestering RAR to the nucleolus in response to RA...
September 25, 2017: Oncogene
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