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chronic myelogenous leukemia

Xiaoyan Liu, Qing Zhou, Yan Xu, Minjiang Chen, Jing Zhao, Mengzhao Wang
Since the introduction of imatinib for the treatment of chronic myelogenous leukemia, several oncogenic mutations have been identified in various malignancies that can serve as targets for therapy. More recently, a deeper insight into the mechanism of antitumor immunity and tumor immunoevasion have facilitated the development of novel immunotherapy agents. Certain targeted agents have the ability of inhibiting tumor growth without causing severe lymphocytopenia and amplifying antitumor immune response by increasing tumor antigenicity, enhancing intratumoral T cell infiltration, and altering the tumor immune microenvironment, which provides a rationale for combining targeted therapy with immunotherapy...
October 17, 2017: Oncotarget
Hu Lei, Jin Jin, Meng Liu, Xiangyun Li, Hao Luo, Li Yang, Hanzhang Xu, Yingli Wu
Drug resistance to tyrosine kinase inhibitors (TKIs) is currently a clinical problem of chronic myelogenous leukemia (CML). Bcr-Abl protein depletion is considered as a way to overcome drug resistance to TKIs. In our study, Chk1 inhibitors, AZD7762 and MK-8776, had strong antitumor effects on CML cell line KBM5 and imatinib-resistant form KBM5(T315I). Moreover, Chk1 inhibitors showed a strong cytotoxic effect on leukemia cells from primary CML and imatinib-resistance CML patients, but low cytotoxic effect on normal human mononuclear cells...
November 11, 2017: Leukemia Research
Natalie Ertz-Archambault, Katalin Kelemen
Based on the current WHO Classification of Myeloid Neoplasms, cytogenetic findings play a central role in the diagnostic classification of the myeloid malignancies. Cytogenetic abnormalities detected at primary diagnosis may change over time. Karyotype changes can be characterized as cytogenetic evolution, cytogenetic regression or a combination of both. While the exact mechanism of cytogenetic evolution is not completely understood, the process of cytogenetic evolution is not random, but follows different, and often disease-specific patterns during progression and relapse of myeloid neoplasms...
December 2017: Panminerva Medica
Ariel E Eber, Alyx Rosen, Kate E Oberlin, Alessio Giubellino, Paolo Romanelli
Tyrosine kinase inhibitors have revolutionized the chemotherapy arena as targeted therapies for a multitude of malignancies. They are more selective than conventional chemotherapy, and often elicit fewer systemic adverse events, however toxicities still exist. Cutaneous toxicities are common and their management presents a novel challenge to physicians and patients. Ponatinib is a third-generation tyrosine kinase inhibitor increasingly reported to cause cutaneous eruption. A 50-year-old woman with a history of chronic myelogenous leukemia presented with a 4-month history of worsening atrophic and ichthyosiform pink plaques involving the axillae, thighs and abdomen; red patches were also observed on the cheeks and forehead...
November 14, 2017: Drug Safety—Case Reports
Jai-Sing Yang, Chao-Ying Lee, Hsin-Chung Cho, Chi-Cheng Lu, Sheng-Chu Kuo, Yen-Fang Wen, Fuu-Jen Tsai, Miau-Rong Lee, Shih-Chang Tsai
ITR‑284 is a carboxamide analog that can inhibit proliferation in human promyelocytic leukemia HL-60 cells. To understand the effects and molecular mechanisms of ITR‑284 in human erythromyeloblastoid leukemia, we treated K562 cells with different concentrations of ITR‑284 (0, 2, 4, 6, 8 and 10 nM) and all-trans retinoic acid (ATRA) (0, 0.1, 0.5, 1, 5 and 10 µM) for 24 h. The IC50 of ITR‑284 was ~10 nM in K562 cells treated for 24 h as determined by MTT assay. May-Grünwald-Giemsa staining and nitro blue tetrazolium (NBT) assays were used to determine cell morphology changes and differentiation after ITR‑284 and ATRA treatment...
November 9, 2017: Oncology Reports
Takuya Hirao, Masashi Yamaguchi, Megumi Kikuya, Hiroji Chibana, Kousei Ito, Shigeki Aoki
Tyrosine kinase inhibitors (TKIs), including imatinib (IM), improve the outcome of chronic myelogenous leukemia (CML) therapy. However, TKI treatment is long-term and can induce resistance to TKIs, which often leads to a poor clinical outcome in CML patients. Here, we examined the effect of continuous IM exposure on intracellular energy metabolism in K562 cells, a human Philadelphia chromosome-positive CML cell line, and its subsequent sensitivity to anti-cancer agents. Contrary to our expectations, we found that continuous IM exposure increased sensitivity to TKIs...
November 9, 2017: Cancer Science
Hongping Min, Miaomiao Niu, Weilin Zhang, Jia Yan, Jiachang Li, Xiying Tan, Bo Li, Mengxiang Su, Bin Di, Fang Yan
Development of multidrug resistance (MDR) is a continuous clinical challenge partially due to the overexpression of P-glycoprotein (P-gp) for chronic myelogenous leukemia (CML) patients. Herein, we evaluated the inhibitory potency of emodin, a natural anthraquinone derivative isolated from Rheum palmatum L, on P-gp in P-gp positive K562/ADM cells. Competition experiments combined with molecular docking analysis were utilized to investigate the binding modes between emodin and binding sites of P-gp. Emodin reversed adriamycin resistance in K562/ADM cells accompanied with the decrease of P-gp protein expression, further increasing the uptake of rhodamine123 in both K562/ADM and Caco-2 cells, indicating the inhibition of P-gp efflux function...
2017: PloS One
Lin-Hui Hu, Lian-Fang Pu, Dong-Dong Yang, Cui Zhang, Hui-Ping Wang, Yang-Yang Ding, Man-Man Li, Zhi-Min Zhai, Shudao Xiong
The Philadelphia (Ph; BCR-ABL) chromosome originates from a translocation event between chromosomes 9 and 22, and results in the BCR-ABL fusion gene. In chronic myelogenous leukemia (CML), the BCR-ABL gene is mainly coded for by a major breakpoint cluster region (M-bcr, e13a2 and e14a2). However, in some patients, BCR-ABL genes are encoded by a minor (m)-bcr, e1a2, and a micro (µ)-bcr region, e19a2. These transcripts revealed a different clinical course. The present study described a CML patient whose cytogenetics and FISH analyses of bone marrow revealed a karyotype of 46, XY t(9,22) (q34;q11), while the commercial kits of quantitative PCR (qPCR) failed to detect the BCR-ABL fusion gene...
November 2017: Oncology Letters
San-Yuan Chen, Chun-Hsiang Lin, Jiun-Tsai Lin, Yi-Fang Cheng, Han-Min Chen, Shao-Hsuan Kao
AMP-activated protein kinase (AMPK) is known as a pivotal regulator of cellular metabolism. Mounting evidences have demonstrated that AMPK activation exerts tumor suppressive activity on leukemia cells. The present study reported that adenine, an AMPK activator, triggers cell cycle arrest and autophagy of human chronic myelogenous leukemia K562 cells consequently suppressing cell viability. The present findings revealed that adenine treatment (4.0-8.0 mM) significantly inhibited the viability of K562 cells to 69...
November 2017: Oncology Letters
Fengli Yuan, Liang Qiao, Yinghan Chen, Xin Qi, Yankai Liu, Dehai Li, Qianqun Gu, Jing Li, Ming Liu
AS1041 is a novel synthesized anthraquinone lactone derivative of marine natural compound aspergiolide A (ASP-A) with new structure skeleton and marked cytotoxicity in cancer cells. To study its cytotoxicity in detail, we evaluated its activity on human K562 chronic myelogenous leukemia cells and investigated the related molecule mechanisms. AS1041 significantly inhibited the proliferation and colony formation of K562 cells. Moreover, AS1041 arrested cell cycle progression at G2/M phase in a concentration-dependent manner, and also caused concentration- and time-dependent induction of apoptosis...
November 4, 2017: Marine Drugs
Ryan R Riahi, Philip R Cohen
Dasatinib is an oral tyrosine kinase inhibitor approved for imatinib-resistant chronic myelogenous leukemia. It has been investigated in treating other neoplasms, including non-small-cell lung cancer and a subset of melanomas. Seborrheic dermatitis is characterized by erythematous patches or plaques with scaling typically affecting the external ear, glabella, hair-bearing areas of the face, nasolabial fold, and scalp. Antitumor agents are often associated with mucocutaneous side effects, including seborrheic dermatitis...
July 2017: Journal of Clinical and Aesthetic Dermatology
Junxia Wang, Wuli Zhao, Hong Liu, Hongwei He, Rongguang Shao
Human myofibrillogenesis regulator 1 (MR-1) is a functional gene also known as paroxysmal nonkinesigenic dyskinesia (PNKD). It is localized on human chromosome 2q35, and three different isomers, MR-1L, MR-1M, and MR-1S, are formed by alternative splicing. MR-1S promotes cardiac hypertrophy and is closely related to cancer. MR-1S is overexpressed in hematologic and solid malignancies, such as hepatoma, breast cancer, and chronic myelogenous leukemia. MR-1S causes disordered cell differentiation, initiates malignant transformation and accelerates metastasis...
November 6, 2017: Journal of Drug Targeting
Meg Franklin, Leah Burns, Samuel Perez, Deepak Yerragolam, Dinara Makenbaeva
OBJECTIVE: Evaluate the incidence of Type 2 Diabetes Mellitus (T2DM) and hyperlipidemia (HLD) in CML patients initiating therapy with dasatinib or nilotinib. METHODS: Retrospective study using MarketScan claims from 1/2006-12/2014. The first analysis evaluated occurrence of T2DM, defined as ≥2 claims with a T2DM ICD-9 code or 1 diagnosis claim and an anti-diabetic medication. The second analysis evaluated occurrence of HLD, defined as ≥2 claims with an HLD ICD-9 code, or 1 diagnosis claim and an anti-HLD medication...
November 2, 2017: Current Medical Research and Opinion
H X Sheng, L N Zhou, J L Chen, G L Hu, Q H Wang, D G Gao, L Liao, Y Yang, T Sun, H Chen, B Zhang
No abstract text is available yet for this article.
September 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Khaldoon Alsamman, Xiuli Zhang, Chittibabu Vatte, Mohammad Al Hamad, Omar S El-Masry, Amani Y Owaidah, Faisal Alzahrani, Yao Lin
Involvement of the Interferon Regulatory Factor 1 (IRF-1) gene in regulation of cell differentiation and proliferation made it a potential target in cancer research. IRF-1 acts as a tumor suppressor gene, and is inactivated in chronic (CML) and non-chronic myelogenous leukemia (non-CML). In the light of numerous reports on genetic changes in the noncoding region of the IRF-1 gene, this study aimed to explore possible genomic changes in coding and non-coding regions of IRF-1 in a random sample of leukemic Saudi patients, in order to obtain insights into potential impact of genetic changes on clinicopathological characteristics...
October 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
Jingfeng Zhou, Danian Nie, Juan Li, Xin Du, Yuhong Lu, Yangqiu Li, Chang Liu, Wei Dai, Yun Wang, Yanli Jin, Jingxuan Pan
PURPOSE: Leukemia stem cells (LSCs) are important source of tyrosine kinase inhibitor (TKI) resistance and disease relapse in chronic myelogenous leukemia (CML). Targeting LSCs may be an attractive strategy to override this thorny problem. Given that EZH2 was overexpressed in primary CML CD34+ cells, our purpose in this study was to evaluate the effects of targeting EZH2 on CML LSCs and clarify its underlying mechanism. Experimental Design:Human primary CML CD34+ cells and retrovirally-BCR-ABL-driven CML mouse model were employed to evaluate the effects of suppression of EZH2 by GSK126 or EZH2 specific shRNA in vitro and in vivo...
October 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sun-Hyung Ha, Sung-Koo Kang, Hyunju Choi, Choong-Hwan Kwak, Fukushi Abekura, Jun-Young Park, Kyung-Min Kwon, Hyeun-Wook Chang, Young-Choon Lee, Ki-Tae Ha, Bo Kyeng Hou, Tae-Wook Chung, Cheorl-Ho Kim
The disialic acid-containing glycosphingolipid GD3 recruited membrane transglutaminase 2 (TG2) as a signaling molecule for erythroid differentiation in human chronic myelogenous leukemia (CML) K562 cells. The α1-adrenergic receptor (α1-AR)/TG2-mediated signaling pathway regulated GD3 functions, including gene expression and production, to differentiate CML K562 cells into erythroid lineage cells. Epinephrine, an AR agonist, increased membrane recruitment as well as GTP-photoaffinity of TG2, inducing GD3 synthase gene expression...
September 22, 2017: Oncotarget
Takashi Kumagai, Chiaki Nakaseko, Kaichi Nishiwaki, Chikashi Yoshida, Kazuteru Ohashi, Naoki Takezako, Hina Takano, Yasuji Kouzai, Tadashi Murase, Kosei Matsue, Satoshi Morita, Junichi Sakamoto, Hisashi Wakita, Hisashi Sakamaki, Koiti Inokuchi
Tyrosine kinase inhibitors (TKIs) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMRs); some patients could successfully discontinue TKI therapy after maintaining DMR for ≥1 year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for ≥2 years. This study included 54 patients with CML who were enrolled in D-STOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year consolidation...
October 23, 2017: Cancer Science
Margo MacDonald, Jianxin You
Merkel cell polyomavirus (MCPyV or MCV) is a novel human polyomavirus that has been discovered in Merkel cell carcinoma (MCC), a highly aggressive skin cancer. MCPyV infection is widespread in the general population. MCPyV-associated MCC is one of the most aggressive skin cancers, killing more patients than other well-known cancers such as cutaneous T-cell lymphoma and chronic myelogenous leukemia (CML). Currently, however, there is no effective drug for curing this cancer. The incidence of MCC has tripled over the past two decades...
2017: Advances in Experimental Medicine and Biology
Pamchui Muiwo, Priyatama Pandey, Hafiz M Ahmad, Suganthi S Ramachandran, Alok Bhattacharya
Chronic myelocytic leukemia cell line K562 undergoes differentiation by phorbol esters to megakaryocytes and we have used this system to understand miRNA processing leading to isomiR generation. PMA treatment significantly altered the production of miRNA in K562 cells. Expression of 24.4% of miRNAs were found to be stimulated whereas expression of 10% miRNAs were inhibited by PMA treatment. Our results suggest that miRNA precursors are processed into isomiRs in a deterministic manner. The relative levels of different isomiRs of a miRNA remained mainly unchanged even after PMA treatment irrespective of overall changes in expression (either up-regulation or down-regulation)...
October 16, 2017: Gene
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