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leukemia cancer stem cell

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https://www.readbyqxmd.com/read/28743165/prognostic-factors-and-survival-outcomes-in-patients-with-chronic-myeloid-leukemia-in-blast-phase-in-the-tyrosine-kinase-inhibitor-era-cohort-study-of-477-patients
#1
Preetesh Jain, Hagop M Kantarjian, Ahmad Ghorab, Koji Sasaki, Elias J Jabbour, Graciela Nogueras Gonzalez, Rashmi Kanagal-Shamanna, Ghayas C Issa, Guillermo Garcia-Manero, Devendra Kc, Sara Dellasala, Sherry Pierce, Marina Konopleva, William G Wierda, Srdan Verstovsek, Naval G Daver, Tapan M Kadia, Gautam Borthakur, Susan O'Brien, Zeev Estrov, Farhad Ravandi, Jorge E Cortes
BACKGROUND: Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era. METHODS: A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival...
July 25, 2017: Cancer
https://www.readbyqxmd.com/read/28742454/lenalidomide-maintenance-after-autologous-stem-cell-transplantation-in-newly-diagnosed-multiple-myeloma-a-meta-analysis
#2
Philip L McCarthy, Sarah A Holstein, Maria Teresa Petrucci, Paul G Richardson, Cyrille Hulin, Patrizia Tosi, Sara Bringhen, Pellegrino Musto, Kenneth C Anderson, Denis Caillot, Francesca Gay, Philippe Moreau, Gerald Marit, Sin-Ho Jung, Zhinuan Yu, Benjamin Winograd, Robert D Knight, Antonio Palumbo, Michel Attal
Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myélome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis...
July 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#3
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28730166/impact-of-chromosomal-rearrangement-upon-dna-methylation-patterns-in-leukemia
#4
Hyang-Min Byun, Shahrooz Eshaghian, Dan Douer, Jonathen Trent, Guillermo Garcia-Manero, Ravi Bhatia, Kim Siegmund, Allen S Yang
Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST)...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28718412/stem-cells-cancer-and-musashi-in-blood-and-guts
#5
REVIEW
Michael G Kharas, Christopher J Lengner
The mammalian MSI family of RNA-binding proteins (RBPs) have important roles as oncoproteins in an array of tumor types, including leukemias, glioblastomas, and pancreatic, breast, lung, and colorectal cancers. The mammalian Msi genes, Msi1 and Msi2, have been most thoroughly investigated in two highly proliferative tissues prone to oncogenic transformation: the hematopoietic lineage and the intestinal epithelium. Despite their vast phenotypic differences, MSI proteins appear to have an analogous role in governing the stem cell compartment in both of these tissues, potentially providing a paradigm for a broader understanding of MSI function and oncogenic activities...
May 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28700942/a-pml-slit-axis-controls-physiological-cell-migration-and-cancer-invasion-in-the-cns
#6
Valeria Amodeo, Deli A, Joanne Betts, Stefano Bartesaghi, Ying Zhang, Angela Richard-Londt, Matthew Ellis, Rozita Roshani, Mikaella Vouri, Sara Galavotti, Sarah Oberndorfer, Ana Paula Leite, Alan Mackay, Aikaterini Lampada, Eva Wessel Stratford, Ningning Li, David Dinsdale, David Grimwade, Chris Jones, Pierluigi Nicotera, David Michod, Sebastian Brandner, Paolo Salomoni
Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28698860/genomic-profiling-of-chronic-myelogenous-leukemia-basic-and-clinical-approach
#7
REVIEW
Aliasghar Keramatinia, Alireza Ahadi, Mohammad Esmaeil Akbari, Maryam Mohseny, Alireza Mosavi Jarahi, Narjes Mehrvar, Neda Mansouri, S A Mortazavi Tabatabaei, Abolfazl Movafagh
Chronic myeloid leukemia (CML) is a hematological stem cell cancer driven by BCR-ABL1 fusion protein. We review the previous and recent evidence on the significance of CML in diagnostic and clinic management. The technical monitoring of BCR-ABL1 with quantitative real time-PCR has been used in assessing patient outcome. The cytogenetic mark of CML is Philadelphia chromosome, that is formed by reciprocal chromosomal translocations between human chromosome 9 and 22, t(9:22) (q(34):q(11)). It makes a BCR-ABL1 fusion protein with an anomaly tyrosine kinase activity that promotes the characteristic proliferation of progenitor cells in CML and acute lymphoblastic lymphoma...
June 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28693523/inhibition-of-lin28b-impairs-leukemia-cell-growth-and-metabolism-in-acute-myeloid-leukemia
#8
Jianbiao Zhou, Chonglei Bi, Ying Qing Ching, Jing-Yuan Chooi, Xiao Lu, Jessie Yiying Quah, Sabrina Hui-Min Toh, Zit-Liang Chan, Tuan Zea Tan, Phyllis Sy Chong, Wee-Joo Chng
BACKGROUND: Current conventional chemotherapy for acute myeloid leukemia (AML) can achieve remission in over 70% of patients, but a majority of them will relapse within 5 years despite continued treatment. The relapse is postulated to be due to leukemia stem cells (LSCs), which are different from normal hematopoietic stem cells (HSCs). LIN28B is microRNA regulator and stem cell reprogramming factor. Overexpression of LIN28B has been associated with advance human malignancies and cancer stem cells (CSCs), including AML...
July 11, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28690187/evaluating-of-oct-4-and-nanog-was-differentially-regulated-by-a-new-derivative-indole-in-leukemia-cell-line
#9
Mojgan Noroozi Karimabad, Mehdi Mahmoodi, Abdollah Jafarzadeh, Ali Darehkordi, Mohammad Reza Hajizadeh, Hossein Khorramdelazad, Ahmad Reza Sayadi, Fariba Rahmani, Gholamhossein Hassanshahi
BACKGROUND: The potential exists to improve treatment through characterization of tumor stem cells and identification of therapeutic targets Using OCT-4 and NANOG genes. Here we have synthesized and investigated the potential of; New Indole-3-carbaldehyde derivative (NI-3-CD) in inhibiting the expression of self-renewal regulatory factors and cancer stem cell gene in a leukemia cell line NB4. METHODOLOGY: The NB4 cells were cultured in RPMI1640 medium contained NI-3-CD and I3F (15...
July 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28679300/the-emerging-role-of-immune-checkpoint-based-approaches-in-aml-and-mds
#10
Prajwal Boddu, Hagop Kantarjian, Guillermo Garcia-Manero, James Allison, Padmanee Sharma, Naval Daver
The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28679298/prevalence-of-cutaneous-viral-infections-in-incident-cutaneous-squamous-cell-carcinoma-detected-among-chronic-lymphocytic-leukemia-and-hematopoietic-stem-cell-transplant-patients
#11
Shalaka S Hampras, Frederick L Locke, Julio C Chavez, Nishit S Patel, Anna R Giuliano, Kyle Miller, Tarik Gheit, Massimo Tommasino, Dana E Rollison
The role of cutaneous viral infections in the development of non-melanoma skin cancer (NMSC), including cutaneous squamous cell carcinoma (SCC), among chronic lymphocytic leukemia (CLL) and blood and marrow transplant (BMT) patients is not established. CLL (n = 977) and BMT (n = 3587) patients treated at the Moffitt Cancer Center were included in a retrospective cohort study. Human papillomavirus (HPV) and human polyomavirus (HPyV) DNA were examined in a subset of incident SCC tumors. Five-year cumulative incidence of NMSC was 1...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28677814/involvement-of-mitochondrial-dynamics-in-the-antineoplastic-activity-of-cisplatin-in-murine-leukemia-l1210-cells
#12
Xiao-Jian Han, Sheng-Lan Shi, Yong-Fang Wei, Li-Ping Jiang, Miao-Yu Guo, Hong-Li Wu, Yu-Ying Wan
Leukemia is a type of hematopoietic stem cell malignant cloned disease with high mortality. Cisplatin-based chemotherapy is one of the most common treatments for leukemia. Similar to other chemotherapeutic agents, cisplatin resistance has become a serious issue in cancer therapy. In the present study, we investigated the role of mitochondrial dynamics in the antineoplastic activity of cisplatin in murine leukemia L1210 cells. Firstly, the L1210 cell line resistant to cisplatin (L1210/DDP) was established. Compared to its parental cell line, the IC50 value of cisplatin in the L1210/DDP cells was increased 10-fold...
August 2017: Oncology Reports
https://www.readbyqxmd.com/read/28676668/the-calreticulin-calr-exon-9-mutations-are-promising-targets-for-cancer-immune-therapy
#13
M O Holmström, E Martinenaite, S M Ahmad, Ö Met, C Friese, L Kjær, C H Riley, P Thor Straten, I M Svane, H C Hasselbalch, M H Andersen
The CALR exon 9 mutations are found in approximately 30% of patients with essential thrombocythemia and primary myelofibrosis. Recently, we reported spontaneous immune responses against the CALR mutations. Here, we describe that CALR-mutant (CALRmut)-specific T-cells are able to specifically recognize CALRmut cells. First, we established a T-cell culture specific for a CALRmut epitope. These specific T-cells were able to recognize several epitopes in the CALRmut C-terminus. Next, we established a CALRmut specific CD4(+) T-cell clone by limiting dilution...
July 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28674830/evidence-for-a-pre-existing-telomere-deficit-in-non-clonal-hematopoietic-stem-cells-in-patients-with-acute-myeloid-leukemia
#14
Mónica S Ventura Ferreira, Martina Crysandt, Patrick Ziegler, Sebastian Hummel, Stefan Wilop, Martin Kirschner, Mirle Schemionek, Edgar Jost, Wolfgang Wagner, Tim H Brümmendorf, Fabian Beier
Telomere shortening represents an established mechanism connecting aging and cancer development. We sequentially analyzed telomere length (TL) of 49 acute myeloid leukemia (AML) patients at diagnosis (n = 24), once they achieved complete cytological remission (CCR) and/or during refractory disease or relapse and after 1-year follow-up, with all patients having at least two sequential samples. TL was analyzed by monochrome multiplex quantitative polymerase chain reaction. We have observed substantially shortened TL in the cells of patients at diagnosis compared to age-adjusted controls...
July 3, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28670499/wnt-signaling-pathway-protein-lef1-in-cancer-as-a-biomarker-for-prognosis-and-a-target-for-treatment
#15
REVIEW
Larion Santiago, Garrett Daniels, Dongwen Wang, Fang-Ming Deng, Peng Lee
Transcription factors are regulatory proteins that either activate or repress the transcription of genes via binding to DNA regulatory sequences and regulating recruitment of transcriptional complexes. Lymphoid enhancer-binding factor 1 (LEF1), a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a downstream mediator of the Wnt/β-catenin signaling pathway, but can also modulate gene transcription independently. LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28665981/ha117-endows-hl60-cells-with-a-stem-like-signature-by-inhibiting-the-degradation-of-dnmt1-via-its-ability-to-down-regulate-expression-of-the-ggl-domain-of-rgs6
#16
Shuangshuang Li, Xianqing Jin, Huan Wu, Yi Wang, Xiaoqing Li, Yuxia Guo, Shaoyan Liang
All-trans retinoic acid (ATRA) induces complete remission in almost all patients with acute promyelocytic leukemia (APL) via its ability to induce the in vivo differentiation of APL blasts. However, prolonged ATRA treatment can result in drug resistance. In previous studies, we generated a multi-drug-resistant HL60/ATRA cell line and found it to contain a new drug resistance-related gene segment, HA117. In this study, we demonstrate that ATRA induces multi-drug-resistant subpopulations of HL60 cells with a putative stem-like signature by up-regulating the expression of the new gene segment HA117...
2017: PloS One
https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#17
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
BACKGROUND & AIMS: We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS: We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses...
June 22, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28645468/aldhs-in-normal-and-malignant-hematopoietic-cells-potential-new-avenues-for-treatment-of-aml-and-other-blood-cancers
#18
Maura Gasparetto, Clayton A Smith
Multiple studies have demonstrated that ALDH1A1 is elevated in hematopoietic stem cells (HSCs). As a means to better characterize such cells, we previously developed the fluorescent ALDH1A1 substrate Aldefluor to facilitate HSC identification and isolation. This has proven useful for counting and isolating HSCs from human bone marrow, peripheral blood and cord blood as well as stem cells in other tissues and organisms. Given the high level expression of ALDH1A1, we explored its biology and that of other ALDHs in HSCs and found that ALDH1A1 and ALDH3A1 were important in metabolizing reactive aldehydes (RAlds) and reactive oxygen species (ROS)...
June 20, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28641990/do-negative-emotions-expressed-during-follow-up-consultations-with-adolescent-survivors-of-childhood-cancer-reflect-late-effects
#19
Anneli V Mellblom, Ellen Ruud, Jon Håvard Loge, Hanne C Lie
OBJECTIVE: To explore whether negative emotions expressed by adolescent cancer survivors during follow-up consultations were associated with potential late effects (persisting disease or treatment-related health problems). METHODS: We video-recorded 66 follow-up consultations between 10 pediatricians and 66 adolescent survivors of leukemia, lymphoma or stem-cell transplantations. In transcripts of the recordings, we identified utterances coded as both 1) expressions of negative emotions (VR-CoDES), and 2) late effect-related discussions...
June 14, 2017: Patient Education and Counseling
https://www.readbyqxmd.com/read/28640831/ribosomal-dna-copy-number-loss-and-sequence-variation-in-cancer
#20
Baoshan Xu, Hua Li, John M Perry, Vijay Pratap Singh, Jay Unruh, Zulin Yu, Musinu Zakari, William McDowell, Linheng Li, Jennifer L Gerton
Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with mapping and analysis. We applied computational and droplet digital PCR approaches to measure rDNA copy number in normal and cancer states in human and mouse genomes. We find that copy number and sequence can change in cancer genomes...
June 2017: PLoS Genetics
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