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Leukemia biomarker

Rajab Mardani, Mohammad Hassan Jafari Najaf Abadi, Mahsa Motieian, Sima Taghizadeh-Boroujeni, Amir Bayat, Alireza Farsinezhad, Seyed Mohammad Gheibi Hayat, Mahtab Motieian, Hossein Pourghadamyari
Leukemia is known as a progressive malignant disease, which destroys the blood-forming organs and results in adverse effects on the proliferation and development of leukocytes and their precursors in the blood and bone marrow. There are four main classes of leukemia including acute leukemia, chronic leukemia, myelogenous leukemia, and lymphocytic leukemia. Given that a variety of internal and external factors could be associated with the initiation and progression of different types of leukemia. One of the important factors is epigenetic regulators such as microRNAs (miRNAs) and long noncoding RNAs (ncRNA)...
December 4, 2018: Journal of Cellular Physiology
Christian Brieghel, Savvas Kinalis, Christina W Yde, Ane Y Schmidt, Lars Jønson, Michael A Andersen, Caspar da Cunha-Bang, Lone B Pedersen, Christian H Geisler, Finn C Nielsen, Carsten U Niemann
In chronic lymphocytic leukemia, TP53 mutations and deletion of chromosome 17p are well-characterized biomarkers associated with poor progression-free and overall survival following chemoimmunotherapy. Patients harboring low burden TP53 mutations with variant allele frequencies of 0.3-15% have been shown to have similar dismal outcome as those with high burden mutations. We here describe a highly sensitive deep targeted Next Generation Sequencing assay allowing for the detection of TP53 mutations as low as 0...
December 4, 2018: Haematologica
Piers Blombery, Mary Ann Anderson, Jia-Nan Gong, Rachel Thijssen, Richard W Birkinshaw, Ella R Thompson, Charis E Teh, Tamia Nguyen, Zhen Xu, Christoffer Flensburg, Thomas E Lew, Ian J Majewski, Daniel H D Gray, David A Westerman, Constantine S Tam, John F Seymour, Peter E Czabotar, David C S Huang, Andrew W Roberts
The BCL2 inhibitor, venetoclax, induces high rates of durable remission in patients with previously treated chronic lymphocytic leukemia (CLL). However, despite continuous daily treatment, leukemia recurs in most patients. To investigate the mechanisms of secondary resistance, we analyzed paired pre-venetoclax and progression samples from 15 patients with CLL progression enrolled on venetoclax clinical trials. The novel Gly101Val mutation in BCL2 was identified at progression in seven patients, but not at study entry...
December 4, 2018: Cancer Discovery
Xin He, Wenlu Li, Xiaogong Liang, Xuan Zhu, Lei Zhang, Yu Huang, Teng Yu, Shu Li, Zhigang Chen
BACKGROUND/AIMS: IGF2BP2 has been reported to serve as an oncogene in various solid cancers. However, the role of IGF2BP2 in acute myelocytic leukemia (AML) is still unknown. METHODS: Public databases Gene Omnibus was used to evaluate the expression of IGF2BP2 in AML patients and healthy controls. In addition, primary cells from these two populations were prepared by Ficoll density centrifugation. Rt-qPCR and western blot were used to detect IGF2BP2 expression in the primary cells from these two populations...
December 4, 2018: Cellular Physiology and Biochemistry
Pier P Piccaluga, Stefania Paolini, Mohsen Navari, Maryam Etebari, Giuseppe Visani, Stefano Ascani
Myeloid sarcomas (MS) are tumors composed by myeloid elements and developing outside bone marrow. The prognosis is overall poor, only stem cell transplantation being consistently reposted as a potentially curative approach. In this study we explored whether microvessel density, a biomarker of angiogenesis, might be relevant in MS. We studied 60 MS, 24 acute myeloid leukemia, 5 normal bone marrow samples and 2 cases of extramedullary hemopoiesis in patients without evidence of hematological malignancy. We used immunohistochemistry (anti-CD34) to identify and quantify micro-vessel density (MVD) and micro-vessel grading (MVG)...
2018: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
Chan-Young Ock, Heewon Seo, Dae-Yoon Kim, Byung Joo Min, Yoomi Park, Hyun Sub Cheong, Hyung-Lae Kim, Eun-Young Song, Inho Kim, Sung-Soo Yoon, Ju Han Kim, Youngil Koh
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been the only treatment option for acute myeloid leukemia (AML) refractory to induction chemotherapy, with only 10-20% of patients achieving long-term survival. Certain donor genotypes may confer leukemia-clearing effects after allo-HSCT. We performed whole-exome sequencing of five pairs of the germ lines in AML patients who achieved long-term remission after allo-HSCT and in their donors, and found two significant variants: EGFR c.2982C > T and CDH11 c...
December 3, 2018: Leukemia & Lymphoma
Lang Li, Tammy Sajdyk, Ellen M L Smith, Chien Wei Chang, Claire Li, Richard H Ho, Raymond Hutchinson, Elizabeth Wells, Jodi L Skiles, Naomi Winick, Jamie L Renbarger
Vincristine is one of the core chemotherapy agents used in the treatment of pediatric acute lymphoblastic leukemia (ALL). However, one of the major toxicities resulting from vincristine exposure is vincristine-induced peripheral neuropathy (VIPN). When VIPN results in significant morbidity, the vincristine dose may need to be reduced, thus potentially decreasing the effectiveness of treatment. To date there are no robust biomarkers used clinically to determine which patients will be at risk for worse neuropathy...
December 3, 2018: Clinical Pharmacology and Therapeutics
Silin Gan, Ping Ma, Jie Ma, Weimin Wang, Haohao Han, Li Chen, Xue Li, Feifei Wu, Hui Sun
Leukemia is the most frequent malignancy in children with acute myeloid leukemia (AML) as the second commonest type. Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been widely reported as an oncogenic factor in multiple malignancies including AML. However, the roles and molecular mechanisms of ZFAS1 in the tumorigenesis of AML are poor defined till now. In the present study, RT-qPCR assay showed that ZFAS1 was highly expressed in bone marrow of acute leukemia patients and AML cell lines. Loss-of-function analyses revealed that ZFAS1 knockdown inhibited proliferation and promoted apoptosis in AML cells and curbed AML xenograft growth in vivo...
November 28, 2018: European Journal of Pharmacology
Zhang-Yuan Yang, You-Shan Zhang, Cai-Xia Liang, Zheng-Ju Zhou
OBJECTIVE: To analyze the relation between the signle nucleotide polymorphisms (SNP) of CYP3A5 gene and MDR1 gene loci and the risk of cytogenetic relapse in chronic myeloid leukemia (CML). METHODS: The clinical data of 90 patients with CML treated with imatinib in our hospital were collected.The patients were divided into 2 groups: non-relapse and relapse according to relapse and non-relapse, then the relation between the SNP of CYP3A5 gene and MRD1 gene loci and the risk of cytogenetic relapse in CML patients...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Ji Zhang, Yawen Jiang, Xu Han, Mridul Roy, Wenen Liu, Xielan Zhao, Jing Liu
AIM: This study was aimed to investigate the expression profiles and biological function of plasma miRNAs at different phases of chronic myeloid leukemia (CML). MATERIALS & METHODS: Differentially expressed miRNAs were identified by microarray. The candidate miRNAs were validated by quantitative real-time PCR at chronic phase, accelerated phase and blast crisis. The functional analysis of miRNAs was carried out by using DAVID. RESULTS: The putative targets of dysregulated miRNAs were involved in important signaling pathways...
December 3, 2018: Future Oncology
Mohsen Taheri, Jamshid Motalebzadeh, Frouzandeh Mahjoubi
Background: Breast cancer is the most common malignancy in women. Multidrug resistance (MDR) is still a great obstacle of breast cancer chemotherapy. We have previously shown that multidrug resistance-associated protein 1 (MRP1) is associated with response to neoadjuvant chemotherapy. The lung resistance-related protein (LRP) is identified as a prognostic marker and response to treatment factor which has been studied mainly in hematological malignancy and leukemia. In this study, we aimed to analyze LRP expression and possible correlation between the expression level of this gene with MRP1 as a candidate marker for chemotherapy resistance...
November 29, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Canan G Nebigil, Laurent Désaubry
Cardiotoxicity is one of the main adverse effects of chemotheraphy, affecting the completion of cancer therapies and the short- and long-term quality of life. Anthracyclines are currently used to treat many cancers, including the various forms of leukemia, lymphoma, melanoma, uterine, breast, and gastric cancers. World Health Organization registered anthracyclines in the list of essential medicines. However, anthracyclines display a major cardiotoxicity that can ultimately culminate in congestive heart failure...
2018: Frontiers in Pharmacology
Jan Davidson-Moncada, Elena Viboch, Sarah E Church, Sarah E Warren, Sergio Rutella
Acute myeloid leukemia (AML) is a molecularly heterogeneous hematological malignancy with variable response to treatment. Recurring cytogenetic abnormalities and molecular lesions identify AML patient subgroups with different survival probabilities; however, 50⁻70% of AML cases harbor either normal or risk-indeterminate karyotypes. The discovery of better biomarkers of clinical success and failure is therefore necessary to inform tailored therapeutic decisions. Harnessing the immune system against cancer with programmed death-1 (PD-1)-directed immune checkpoint blockade (ICB) and other immunotherapy agents is an effective therapeutic option for several advanced malignancies...
November 25, 2018: Biomedicines
Y Wang, Y Li, H-Q Song, G-W Sun
OBJECTIVE: Recently, several long non-coding RNAs (lncRNAs) have been implicated in acute myeloid leukemia (AML). However, the clinical significance of lncRNAs in AML patients still remains unclear. We aimed to evaluate the expression level of lncRNA LINC00899 (LINC00899) and its potential for diagnosis and prognosis in AML. PATIENTS AND METHODS: Expression levels of LINC00899 in bone marrow and serum obtained from AML patients and healthy controls were assessed by quantitative real-time PCR...
November 2018: European Review for Medical and Pharmacological Sciences
Nonthaphat Kent Wong, Chien-Ling Huang, Rashidul Islam, Shea Ping Yip
Recent studies have revealed that non-coding regions comprise the vast majority of the human genome and long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs that has been implicated in a variety of biological processes. Abnormal expression of lncRNAs has also been linked to different human diseases including cancers, yet the regulatory mechanisms and functional effects of lncRNAs are still ambiguous, and the molecular details also need to be confirmed. Unlike protein-coding gene, it is much more challenging to unravel the roles of lncRNAs owing to their unique and complex features such as functional diversity and low conservation among species, which greatly hamper their experimental characterization...
November 22, 2018: Journal of Hematology & Oncology
Lan Yang, Jing-Dong Zhou, Ting-Juan Zhang, Ji-Chun Ma, Gao-Fei Xiao, Qin Chen, Zhao-Qun Deng, Jiang Lin, Jun Qian, Dong-Ming Yao
Background and purpose: Abundant studies have shown that lncRNA PANDAR plays an oncogenic role in human solid tumors. Although abnormal expression of PANDAR has been well investigated in solid tumors, it was rarely studied in hematologic diseases. Hence, the aim of this study was to determine the PANDAR expression level and its clinical significance in patients with acute myeloid leukemia (AML). Materials and methods: For detecting the expression level of PANDAR in 119 AML patients and 26 controls, real-time quantitative PCR was used in this study...
2018: Cancer Management and Research
Jian Li, Yunchao Wang, Jiayun Ge, Wenhua Li, Liangyu Yin, Zhiping Zhao, Songsong Liu, Huan Qin, Jiali Yang, Lijiang Wang, Bing Ni, Yongkang Liu, Huaizhi Wang
BACKGROUND/AIMS: Cancer stem cells (CSCs) are largely responsible for tumor relapse and metastatic behavior. Doublecortin-like kinase 1 (DCLK1) was recently reported to be a biomarker for gastrointestinal CSCs and involved in the epithelial-mesenchymal transition (EMT) and tumor progression. B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) is a crucial regulator of CSC self-renewal, malignant transformation and EMT, and a previous study from our group showed that Bmi-1 is upregulated in pancreatic cancer progression and participates in EMT...
2018: Cellular Physiology and Biochemistry
Ziad Bakouny, Elie El Rassy, Fares Yared, Antoine Abi Lutfallah, Marwan Ghosn, Fadi Farhat, Joseph Kattan
Aim: The rationale for platelet-to-lymphocyte ratio (PLR) in chronic lymphocytic leukemia (CLL) is that both the platelet and lymphocyte counts are affected by the CLL pathogenesis and could influence treatment decision-making. Methods: Demographic and clinical data of CLL patients diagnosed at our institution between 1989 and 2013 were collected. Cox regression models were used to evaluate the role of PLR in the duration of watchful waiting, postdiagnosis survival and postchemotherapy survival...
December 2018: Future Science OA
Yingchao Duan, Wenping Qin, Fengzhi Suo, Xiaoyu Zhai, Yuanyuan Guan, Xiaojuan Wang, Yichao Zheng, Hongmin Liu
LSD1 is implicated in a number of malignancies and has emerged as an exciting target. As part of our sustained efforts to develop novel reversible LSD1 inhibitors for epigenetic therapy of cancers, in this study, we reported a series of stilbene derivatives and evaluated their LSD1 inhibitory activities, obtaining several compounds as potent LSD1 inhibitors with IC50 values in submicromolar range. Enzyme kinetics studies and SPR assay suggested that compound 8c, the most active LSD1 inhibitor (IC50  = 283 nM), potently inhibited LSD1 in a reversible and FAD competitive manner...
October 29, 2018: Bioorganic & Medicinal Chemistry
Chundi Gao, Chao Zhou, Jing Zhuang, Lijuan Liu, Junyu Wei, Cun Liu, Huayao Li, Changgang Sun
Chronic lymphocytic leukemia (CLL) is a malignant clonal proliferative disorder of B cells. Inhibition of cell apoptosis and cell cycle arrest are the main pathological causes of this disease, but its molecular mechanism requires further investigation. The purpose of the present study was to identify biomarkers for the early diagnosis and treatment of CLL, and to explore the molecular mechanisms of CLL progression. A total of 488 differentially expressed genes (DEGs) and 32 differentially expressed microRNAs (miRNAs; DEMs) for CLL were identified by analyzing the gene chips GSE22529, GSE39411 and GSE62137...
November 9, 2018: Molecular Medicine Reports
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