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Leukemia biomarker

Xin-Yue Lian, Ji-Chun Ma, Jing-Dong Zhou, Ting-Juan Zhang, De-Hong Wu, Zhao-Qun Deng, Zhi-Hui Zhang, Xi-Xi Li, Pin-Fang He, Yang Yan, Jiang Lin, Jun Qian
The current study was aimed to investigate integrin beta-like 1 (ITGBL1) methylation pattern and its clinical relevance in patients with acute myeloid leukemia (AML). Real-time methylation-specific polymerase chain reaction (PCR; RQ-MSP) and bisulfite sequencing PCR (BSP) were performed to detect the methylation of ITGBL1 promoter. Real-time quantitative PCR (RT-qPCR) was performed to analyze ITGBL1 transcript level. The results showed that ITGBL1 methylation level in 131 patients with AML was significantly higher than 29 controls (p < 0...
October 14, 2018: Journal of Cellular Physiology
Tadamune Kinjo, Hirosuke Inoue, Takeshi Kusuda, Junko Fujiyoshi, Masayuki Ochiai, Yasushi Takahata, Satoshi Honjo, Yuhki Koga, Toshiro Hara, Shouichi Ohga
BACKGROUND: Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM...
September 24, 2018: Pediatrics and Neonatology
Sophie Paczesny, Jochen Metzger
Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective form of tumor immunotherapy available to date. However, while HSCT can induce beneficial graft-versus-leukemia (GVL) effect, the adverse effect of graft-versus-host disease (GVHD), which is closely linked to GVL, is the major source of morbidity and mortality following HSCT. Until recently, available diagnostic and staging tools frequently fail to identify those at higher risk of disease progression or death. Furthermore, there are shortcomings in the prediction of the need for therapeutic interventions or the response rates to different forms of therapy...
October 11, 2018: Proteomics. Clinical Applications
Phyllis S Y Chong, Jianbiao Zhou, Jing-Yuan Chooi, Zit-Liang Chan, Sabrina Hui Min Toh, Tuan Zea Tan, Sheena Wee, Jayantha Gunaratne, Qi Zeng, Wee-Joo Chng
Aberrant activation of Wnt/β-catenin signaling pathway is essential for the development of AML; however, the mechanistic basis for this dysregulation is unclear. PRL-3 is an oncogenic phosphatase implicated in the development of LSCs. Here, we identified Leo1 as a direct and specific substrate of PRL-3. Serine-dephosphorylated form of Leo1 binds directly to β-catenin, promoting the nuclear accumulation of β-catenin and transactivation of TCF/LEF downstream target genes such as cyclin D1 and c-myc. Importantly, overexpression of PRL-3 in AML cells displayed enhanced sensitivity towards β-catenin inhibition in vitro and in vivo, suggesting that these cells are addicted to β-catenin signaling...
October 10, 2018: Oncogene
Prachi Jain, Xin Tian, Stefan Cordes, Jinguo Chen, Caroline R Cantilena, Christian Bradley, Reema Panjwani, Fariba Chinian, Keyvan Keyvanfar, Minoo Battiwalla, Pawel Muranski, A John Barrett, Sawa Ito
Blockade of the T cell exhaustion marker PD-1 to re-energize the immune response is emerging as a promising cancer treatment. Relapse of hematological malignancy after allogeneic stem cell transplantation (allo-SCT) limits the success of this approach and PD-1 blockade may hold therapeutic promise. However, PD-1 expression and its relationship with post-transplant relapse is poorly described. Since the donor immunity is activated by allo-responses, PD-1 expression may differ from non-transplanted individuals and PD-1 blockade could risk graft-versus-host disease...
October 4, 2018: Biology of Blood and Marrow Transplantation
Bowen Yan, Qinwei Chen, Koji Shimada, Ming Tang, Haoli Li, Aishwarya Gurumurthy, Joseph D Khoury, Bing Xu, Suming Huang, Yi Qiu
Chemoresistance may be due to the survival of leukemia stem cells (LSCs) that are quiescent and not responsive to chemotherapy or lie on the intrinsic or acquired resistance of the specific pool of AML cells. Here, we found, among well-established LSC markers, only CD123 and CD47 are correlated with AML cell chemosensitivities across cell lines and patient samples. Further study reveals that percentages of CD123+ CD47+ cells significantly increased in chemoresistant lines compared to parental cell lines. However, stemness signature genes are not significantly increased in resistant cells...
October 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Xin Li, Juan Pang, Wenwen Xue, Yixuan Wang, Tian Tian, Ahmed Elgehama, Xuefeng Wu, Xudong Wu, Yang Sun, Hongxia Qiu, Yan Shen, Qiang Xu
BCR-ABL kinase mutations, accounting for clinical resistance to tyrosine kinase inhibitor (TKI) such as imatinib, frequently occur in acquired resistance or in advanced phases of chronic myeloid leukemia (CML). Emerging evidence implicates a critical role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. Here, we utilized non-mutational imatinib-resistant K562/G cells to reveal SHP-2 as a resistance modulator of imatinib treatment response during the early phase...
October 2, 2018: Toxicology and Applied Pharmacology
Guillermo Philipps, Elizabeth D Tate, Michael R Pranzatelli
Paraneoplastic cerebellar degeneration is rare and noteworthy in children. In this 7-year-old, it was documented to have occurred within a year of ataxia presentation. The instigating cancer was stage III adrenal adenocarcinoma, remitted after surgical resection at age 2. When her severe ataxia progressed, neuroinflammation was characterized by high cerebrospinal fluid Purkinje cell cytoplasmic antibody type 1 titers, oligoclonal bands, and neurofilament light chain. The immunotherapy strategy was to replace IV methylprednisolone, which lowered Purkinje cell cytoplasmic antibody type 1 titers without clinical improvement, with induction of adrenocorticotropic hormone/intravenous immunoglobulin/rituximab (ACTH/IVIG/rituximab) combination immunotherapy, ACTH/dexamethasone transition, and intravenous immunoglobulin maintenance...
2018: Child Neurology Open
Chen Yang, Tingting Shao, Huihui Zhang, Ninghan Zhang, Xiaoying Shi, Xuejiao Liu, Yao Yao, Linyan Xu, Shengyun Zhu, Jiang Cao, Hai Cheng, Zhiling Yan, Zhenyu Li, Mingshan Niu, Kailin Xu
BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous disease. MicroRNAs function as important biomarkers in the clinical prognosis of AML. METHODS: This study identified miR-425 as a prognostic factor in AML by screening the TCGA dataset. A total of 162 patients with AML were enrolled for the study and divided into chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) groups. RESULTS: In the chemotherapy group, patients with high miR-425 expression had significantly longer overall survival (OS) and event-free survival (EFS) compared with patients with low miR-425 expression...
October 1, 2018: Journal of Translational Medicine
Sourav Mishra, Yoonhee Lee, Joon Won Park
Molecular monitoring is indispensable for the clinical management of chronic myeloid leukemia (CML) patients. Real-time quantitative polymerase chain reaction (RT-qPCR) is the gold standard for the quantitative assessment of BCR-ABL transcript levels, which are critical in clinical decision-making. However, the frequent recurrence of the disease after drug discontinuation for 60% of patients has necessitated more sensitive and specific techniques to detect residual BCR-ABL transcripts. Here, we describe a quantification method for the detection of BCR-ABL targets at very low concentrations (< 10 copies/sample) in the presence of a million copies of normal BCR and ABL genes...
October 1, 2018: Analytical Chemistry
Wencheng Zhao, Lin Wang, Yongbin Yu
Juvenile myelomonocytic leukemia (JMML) is a rare but severe primary hemopoietic system tumor of childhood, most frequent in children 4 years and younger. There are currently no specific anticancer therapies targeting JMML, and the underlying gene expression changes have not been revealed. To define molecular targets and possible biomarkers for early diagnosis, optimal treatment, and prognosis, we conducted microarray data analysis using the Gene Expression Omnibus, and constructed protein‑protein interaction networks of all differentially expressed genes...
September 18, 2018: Oncology Reports
Julie A Wolfson, Joshua S Richman, Can-Lan Sun, Wendy Landier, Karen Leung, Eileen P Smith, Margaret O'Donnell, Smita Bhatia
Background: Adolescents and young adults (AYA: 15-39 years) with acute lymphoblastic leukemia (ALL) have inferior survival when compared with children (1-14 years). An approach is lacking that includes both patients enrolled and not enrolled in clinical trials, and includes the contribution of health care delivery, treatment, and clinical prognosticators. Methods: We assembled a retrospective cohort of ALL patients diagnosed between 1-39 years (AYA: n = 93; child: n = 91) and treated at a single institution between 1990 and 2010, irrespective of clinical trial enrollment...
October 2018: Cancer Epidemiology, Biomarkers & Prevention
Lisa S Chen, Prithviraj Bose, Nichole D Cruz, Yongying Jiang, Qi Wu, Philip A Thompson, Shuju Feng, Michael H Kroll, Wei Qiao, Xuelin Huang, Nitin Jain, William G Wierda, Michael J Keating, Varsha Gandhi
Ibrutinib is highly efficacious and used at 420 mg/d for treatment of chronic lymphocytic leukemia (CLL). We previously demonstrated a decline in BTK protein levels in CLL cells after 1 cycle of ibrutinib, suggesting that ibrutinib dose could be lowered after the first cycle without loss of biological effect. To test this postulate, a pilot study (NCT02801578) was designed to systematically reduce ibrutinib dosing within the same patient with CLL over three 28-day cycles. Following an initial cycle of 420 mg/d, the dose was reduced to 280 mg/d in cycle 2 and then to 140 mg/d in cycle 3...
September 25, 2018: Blood
Ruiqi Zhu, Wenyi Lin, Weiwei Zhao, Fengjuan Fan, Liang Tang, Yu Hu
Acute myeloid leukemia (AML) is a hematologic malignancy with significant molecular heterogeneity. MicroRNAs (miRNAs) play a critical role in AML diagnosis, pathogenesis, and prognosis of AML. Little has been done to identify a miRNA signature in pediatric and adolescent patients for predicting overall survival. This study aims to identify a panel of miRNA signature that could predict the prognosis of all younger AML patients with all subtypes of AML by analyzing data from The Cancer Genome Atlas (TCGA). A total of 229 patients under 23 years with miRNA data and corresponding clinical data from TCGA database were enrolled in this study...
September 22, 2018: Journal of Cellular Biochemistry
Monika Drobna, Bronisława Szarzyńska-Zawadzka, Patrycja Daca-Roszak, Maria Kosmalska, Roman Jaksik, Michał Witt, Małgorzata Dawidowska
Optimal endogenous controls enable reliable normalization of microRNA (miRNA) expression in reverse-transcription quantitative PCR (RT-qPCR). This is particularly important when miRNAs are considered as candidate diagnostic or prognostic biomarkers. Universal endogenous controls are lacking, thus candidate normalizers must be evaluated individually for each experiment. Here we present a strategy that we applied to the identification of optimal control miRNAs for RT-qPCR profiling of miRNA expression in T-cell acute lymphoblastic leukemia (T-ALL) and in normal cells of T-lineage...
September 20, 2018: International Journal of Molecular Sciences
Fumitaka Koga, Kosuke Takemura, Hiroshi Fukushima
Chemoradiation-based bladder preservation therapy (BPT) is currently a curative option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at favorable risk or an alternative to radical cystectomy (RC) for those who are unfit for RC. In BPT, only patients who achieve complete response (CR) after chemoradiation have a favorable prognosis and quality of life with a preserved functional bladder. Thus, predicting CR and favorable prognosis is important for optimal patient selection for BPT. We reviewed biomarkers for predicting the clinical outcomes of chemoradiation-based BPT...
September 15, 2018: International Journal of Molecular Sciences
Ina Nepstad, Kimberley Joanne Hatfield, Tor Henrik Anderson Tvedt, Håkon Reikvam, Øystein Bruserud
Clonal heterogeneity detected by karyotyping is a biomarker associated with adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. We suggest that this pathway reflects biologically important clonal heterogeneity. We investigated constitutive PI3K-Akt-mTOR pathway activation in primary human AML cells derived from 114 patients, together with 18 pathway mediators...
September 14, 2018: Cancers
Zhen Zhang, Lin Zhao, Xijin Wei, Qiang Guo, Xiaoxiao Zhu, Ran Wei, Xunqiang Yin, Yunhong Zhang, Bin Wang, Xia Li
Myeloid disorders, especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), cause significant mobility and high mortality worldwide. Despite numerous attempts, the common molecular events underlying the development of MDS and AML remain to be established. In the present study, 18 microarray datasets were selected, and a meta-analysis was conducted to identify shared gene signatures and biological processes between MDS and AML. Using NetworkAnalyst, 191 upregulated and 139 downregulated genes were identified in MDS and AML, among which, PTH2R, TEC , and GPX1 were the most upregulated genes, while MME, RAG1 , and CD79B were mostly downregulated...
October 2018: Oncology Letters
Vladimir Gasic, Branka Zukic, Biljana Stankovic, Dragana Janic, Lidija Dokmanovic, Jelena Lazic, Nada Krstovski, Vita Dolzan, Janez Jazbec, Sonja Pavlovic, Nikola Kotur
Background Response to glucocorticoid (GC) monotherapy in the initial phase of remission induction treatment in childhood acute lymphoblastic leukemia (ALL) represents important biomarker of prognosis and outcome. We aimed to study variants in several pharmacogenes (NR3C1, GSTs and ABCB1) that could contribute to improvement of GC response through personalization of GC therapy. Methods Retrospective study enrolling 122 ALL patients was carried out to analyze variants of NR3C1 (rs33389, rs33388 and rs6198), GSTT1 (null genotype), GSTM1 (null genotype), GSTP1 (rs1695 and rs1138272) and ABCB1 (rs1128503, rs2032582 and rs1045642) genes using PCR-based methodology...
September 11, 2018: Radiology and Oncology
Mihyang Ha, Ji-Young Kim, Myoung-Eun Han, Ga Hyun Kim, Si Young Park, Dae Cheon Jeong, Sae-Ock Oh, Yun Hak Kim
BACKGROUND: Certain nuclear envelope proteins are associated with important cancer cell characteristics, including migration and proliferation. Abnormal expression of and genetic changes in nuclear envelope proteins have been reported in acute myeloid leukemia (AML) patients. Transmembrane protein 18 (TMEM18), a nuclear envelope protein, is involved in neural stem cell migration and tumorigenicity. METHODS: To examine the prognostic significance of TMEM18 in AML patients, we analyzed an AML cohort from The Cancer Genome Atlas (TCGA, n = 142)...
September 10, 2018: Acta Haematologica
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