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https://www.readbyqxmd.com/read/29785257/pure-erythroid-leukemia-in-a-polymyositis-patient-treated-with-azathioprine
#1
Osamu Imataki, Akihiro Takeuchi, Shumpei Uchida, Shigeyuki Yokokura, Makiko Uemura, Norimitsu Kadowaki
Acute erythroid leukemia, also known as acute myeloid leukemia-M6, may be associated with previous chemotherapy or immunosuppressive therapy. For 10 years, a 69-year-old Japanese female patient with pure erythroid leukemia (or acute myeloid leukemia-M6b) was treated for polymyositis with 50-100 mg/day azathioprine. She complained of dyspnea with low-grade fever and was diagnosed as having pure erythroid leukemia. Chromosomal analysis revealed a complex karyotype abnormality, with the deletion of 5q, -6, -7 and addition of 11q13...
2018: Rare Tumors
https://www.readbyqxmd.com/read/29777171/mll-fusion-driven-leukemia-requires-setd2-to-safeguard-genomic-integrity
#2
Anna Skucha, Jessica Ebner, Johannes Schmöllerl, Mareike Roth, Thomas Eder, Adrián César-Razquin, Alexey Stukalov, Sarah Vittori, Matthias Muhar, Bin Lu, Martin Aichinger, Julian Jude, André C Müller, Balázs Győrffy, Christopher R Vakoc, Peter Valent, Keiryn L Bennett, Johannes Zuber, Giulio Superti-Furga, Florian Grebien
MLL-fusions represent a large group of leukemia drivers, whose diversity originates from the vast molecular heterogeneity of C-terminal fusion partners of MLL. While studies of selected MLL-fusions have revealed critical molecular pathways, unifying mechanisms across all MLL-fusions remain poorly understood. We present the first comprehensive survey of protein-protein interactions of seven distantly related MLL-fusion proteins. Functional investigation of 128 conserved MLL-fusion-interactors identifies a specific role for the lysine methyltransferase SETD2 in MLL-leukemia...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29774136/the-impact-of-mir-9-regulation-in-normal-and-malignant-hematopoiesis
#3
Abbas Khosravi, Shaban Alizadeh, Arsalan Jalili, Reza Shirzad, Najmaldin Saki
MicroRNA-9 (MiR-9) dysregulation has been observed in various cancers. Recently, MiR-9 is considered to have a part in hematopoiesis and hematologic malignancies. However, its importance in blood neoplasms is not yet well defined. Thus, this study was conducted in order to assess the significance of MiR-9 role in the development of hematologic neoplasia, prognosis, and treatment approaches. We have shown that a large number of MiR-9 targets (such as FOXOs, SIRT1, CCND1, ID2, CCNG1, Ets, and NFkB) play essential roles in leukemogenesis and that it is overexpressed in different leukemias...
January 30, 2018: Oncology Reviews
https://www.readbyqxmd.com/read/29772764/the-making-of-leukemia
#4
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29764005/identification-of-novel-functional-variants-of-sin3a-and-srsf1-among-somatic-variants-in-acute-myeloid-leukemia-patients
#5
Jae-Woong Min, Youngil Koh, Dae-Yoon Kim, Hyung-Lae Kim, Jeong A Han, Yu-Jin Jung, Sung-Soo Yoon, Sun Shim Choi
The advent of massively parallel sequencing, also called nextgeneration sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AMLrelated genes...
May 15, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29752743/therapy-related-acute-myeloid-leukemia-and-myelodysplastic-syndrome-among-refractory-germ-cell-tumor-patients
#6
Yuta Inoue, Terukazu Nakamura, Hiroyuki Nakanishi, Masakatsu Oishi, Fumiya Hongo, Koji Okihara, Shinsuke Mizutani, Junya Kuroda, Osamu Ukimura
OBJECTIVES: To analyze cases of therapy-related acute myeloid leukemia and myelodysplastic syndrome diagnosed after chemotherapy for refractory testicular and extragonadal germ cell tumor in our experience. METHODS: A total of 171 consecutive patients who were diagnosed and treated as refractory germ cell tumor and had records of detailed chemotherapy doses between April 1998 and December 2015 were retrospectively reviewed. RESULTS: Four testicular tumor patients (4/171, 2...
May 11, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29752294/utx-promotes-chromatin-remodeling-to-suppress-leukemogenesis
#7
(no author information available yet)
UTX-mediated suppression of myeloid leukemogenesis is independent of its demethylase activity.
May 11, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29752293/the-cis-regulatory-derare-element-regulates-leukemogenesis
#8
(no author information available yet)
DERARE methylation suppresses HOXB gene expression and leukemogenesis to maintain normal hematopoiesis.
May 11, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29740160/new-therapeutic-opportunities-from-dissecting-the-pre-b-leukemia-bone-marrow-microenvironment
#9
Laurence C Cheung, Jennifer Tickner, Anastasia M Hughes, Patrycja Skut, Meegan Howlett, Bree Foley, Joyce Oommen, Julia E Wells, Bo He, Sajla Singh, Grace-Alyssa Chua, Jette Ford, Charles G Mullighan, Rishi S Kotecha, Ursula R Kees
The microenvironments of leukemia and cancer are critical for multiple stages of malignancies, and they are an attractive therapeutic target. While skeletal abnormalities are commonly seen in children with acute lymphoblastic leukemia (ALL) prior to initiating osteotoxic therapy, little is known about the alterations to the bone marrow microenvironment during leukemogenesis. Therefore, in this study, we focused on the development of precursor-B cell ALL (pre-B ALL) in an immunocompetent BCR-ABL1+ model. Here we show that hematopoiesis was perturbed, B lymphopoiesis was impaired, collagen production was reduced, and the number of osteoblastic cells was decreased in the bone marrow microenvironment...
May 8, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29736013/utx-mediated-enhancer-and-chromatin-remodeling-suppresses-myeloid-leukemogenesis-through-noncatalytic-inverse-regulation-of-ets-and-gata-programs
#10
Malgorzata Gozdecka, Eshwar Meduri, Milena Mazan, Konstantinos Tzelepis, Monika Dudek, Andrew J Knights, Mercedes Pardo, Lu Yu, Jyoti S Choudhary, Emmanouil Metzakopian, Vivek Iyer, Haiyang Yun, Naomi Park, Ignacio Varela, Ruben Bautista, Grace Collord, Oliver Dovey, Dimitrios A Garyfallos, Etienne De Braekeleer, Saki Kondo, Jonathan Cooper, Berthold Göttgens, Lars Bullinger, Paul A Northcott, David Adams, George S Vassiliou, Brian J P Huntly
The histone H3 Lys27-specific demethylase UTX (or KDM6A) is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through noncatalytic functions, a property shared with its catalytically inactive Y-chromosome paralog, UTY (or KDM6C). In keeping with this, we demonstrate concomitant loss/mutation of KDM6A (UTX) and UTY in multiple human cancers. Mechanistically, global genomic profiling showed only minor changes in H3K27me3 but significant and bidirectional alterations in H3K27ac and chromatin accessibility; a predominant loss of H3K4me1 modifications; alterations in ETS and GATA-factor binding; and altered gene expression after Utx loss...
May 7, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29727682/retinoid-sensitive-epigenetic-regulation-of-the-hoxb-cluster-maintains-normal-hematopoiesis-and-inhibits-leukemogenesis
#11
Pengxu Qian, Bony De Kumar, Xi C He, Christof Nolte, Madelaine Gogol, Youngwook Ahn, Shiyuan Chen, Zhenrui Li, Hanzhang Xu, John M Perry, Deqing Hu, Fang Tao, Meng Zhao, Yingli Han, Kate Hall, Allison Peak, Ariel Paulson, Chongbei Zhao, Aparna Venkatraman, Andrew Box, Anoja Perera, Jeffrey S Haug, Tari Parmely, Hua Li, Robb Krumlauf, Linheng Li
Hox genes modulate the properties of hematopoietic stem cells (HSCs) and reacquired Hox expression in progenitors contributes to leukemogenesis. Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling genes are predominantly enriched in LT-HSCs, and this coordinate regulation of Hoxb expression is mediated by a retinoid-dependent cis-regulatory element, distal element RARE (DERARE). Deletion of the DERARE reduced Hoxb expression, resulting in changes to many downstream signaling pathways (e...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29726059/two-novel-fusion-genes-aif1l-etv6-and-abl1-aif1l-result-together-with-etv6-abl1-from-a-single-chromosomal-rearrangement-in-acute-lymphoblastic-leukemia-with-prenatal-origin
#12
Julius Lukes, Eliska Potuckova, Lucie Sramkova, Jan Stary, Julia Starkova, Jan Trka, Felix Votava, Jan Zuna, Marketa Zaliova
Fusion genes resulting from chromosomal rearrangements represent a hallmark of childhood acute lymphoblastic leukemia (ALL). Unlike more common fusion genes generated via simple reciprocal chromosomal translocations, formation of the ETV6-ABL1 fusion gene requires 3 DNA breaks and usually results from an interchromosomal insertion. We report a child with ALL in which a single interchromosomal insertion led to the formation of ETV6-ABL1 and two novel fusion genes: AIF1L-ETV6 and ABL1-AIF1L. We demonstrate the prenatal origin of this complex chromosomal rearrangement, which apparently initiated the leukemogenic process, by successful backtracking of the ETV6-ABL1 fusion into the patient's archived neonatal blood...
May 4, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29725423/role-of-a-non-canonical-splice-variant-of-the-helios-gene-in-the-differentiation-of-acute-lymphoblastic-leukemic-t-cells
#13
Yinghui Li, Yanhua Liu, Can Liu, Fengyong Liu, Daolei Dou, Wenjie Zheng, Wei Liu, Feifei Liu
T-cell acute lymphoblastic leukemia is a hematopoietic malignant disease, which arises from a genetic defect in the T-cell maturation signaling pathway. As a result, it is necessary to identify the molecules that impact T-cell development and control lymphoid-lineage malignancy. The present study utilized Jurkat T lymphoblastic cells as a well-established approach for the investigation into the function of the non-canonical alternative splice variant of Helios for the in vitro study of T-cell differentiation and leukemogenesis...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29724719/mir142-loss-of-function-mutations-derepress-ash1l-to-increase-hoxa-gene-expression-and-promote-leukemogenesis
#14
Maria C Trissal, Terrence N Wong, Juo-Chin Yao, Rahul Ramaswamy, Iris Kuo, Jack D Baty, Yaping Sun, Gloria Jih, Nishi Parikh, Melissa M Berrien-Elliott, Todd A Fehniger, Timothy J Ley, Ivan Maillard, Pavan Reddy, Daniel C Link
Point mutations in the seed sequence of miR-142-3p are present in a subset of AML and in several subtypes of B cell lymphoma. Here we show that mutations associated with AML result both in loss of miR-142-3p function and in decreased miR-142-5p expression. Mir142 loss altered the hematopoietic differentiation of multipotent hematopoietic progenitors, enhancing their myeloid potential while suppressing their lymphoid potential. During hematopoietic maturation, loss of Mir142 increased Ash1l protein expression and consequently resulted in the aberrant maintenance of Hoxa gene expression in myeloid-committed hematopoietic progenitors...
May 3, 2018: Cancer Research
https://www.readbyqxmd.com/read/29721391/a-genetic-ifn-stat1-fas-axis-determines-cd4-t-stem-cell-memory-levels-and-apoptosis-in-healthy-controls-and-adult-t-cell-leukemia-patients
#15
Ricardo Khouri, Gilvanéia Silva-Santos, Tim Dierckx, Soraya Maria Menezes, Daniele Decanine, Kristof Theys, Aline Clara Silva, Lourdes Farré, Achiléa Bittencourt, Massimo Mangino, Mario Roederer, Anne-Mieke Vandamme, Johan Van Weyenbergh
Adult T-cell leukemia (ATL) is an aggressive, chemotherapy-resistant CD4+ CD25+ leukemia caused by HTLV-1 infection, which usually develops in a minority of patients several decades after infection. IFN + AZT combination therapy has shown clinical benefit in ATL, although its mechanism of action remains unclear. We have previously shown that an IFN-responsive FAS promoter polymorphism in a STAT1 binding site (rs1800682) is associated to ATL susceptibility and survival. Recently, CD4 T stem cell memory (TSCM ) Fashi cells have been identified as the hierarchical cellular apex of ATL, but a possible link between FAS, apoptosis, proliferation and IFN response in ATL has not been studied...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29719258/ppm1k-regulates-hematopoiesis-and-leukemogenesis-through-cdc20-mediated-ubiquitination-of-meis1-and-p21
#16
Xiaoye Liu, Feifei Zhang, Yaping Zhang, Xie Li, Chiqi Chen, Meiyi Zhou, Zhuo Yu, Yunxia Liu, Yuzheng Zhao, Xiaoxin Hao, Yabin Tang, Liang Zhu, Ligen Liu, Li Xie, Hao Gu, Hongfang Shao, Fangzhen Xia, Chunrong Yin, Minfang Tao, Jingjing Xie, Cheng Cheng Zhang, Yi Yang, Haipeng Sun, Guo-Qiang Chen, Junke Zheng
In addition to acting as building blocks for biosynthesis, amino acids might serve as signaling regulators in various physiological and pathological processes. However, it remains unknown whether amino acid levels affect the activities of hematopoietic stem cells (HSCs). By using a genetically encoded fluorescent sensor of the intracellular levels of branched-chain amino acids (BCAAs), we could monitor the dynamics of BCAA metabolism in HSCs. A mitochondrial-targeted 2C-type Ser/Thr protein phosphatase (PPM1K) promotes the catabolism of BCAAs to maintain MEIS1 and p21 levels by decreasing the ubiquitination-mediated degradation controlled by the E3 ubiquitin ligase CDC20...
May 1, 2018: Cell Reports
https://www.readbyqxmd.com/read/29716633/targeting-flt3-in-acute-myeloid-leukemia-using-ligand-based-chimeric-antigen-receptor-engineered-t-cells
#17
Ying Wang, Yingxi Xu, Saisai Li, Jia Liu, Yanyan Xing, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Min Wang, Jianxiang Wang
BACKGROUND: Chimeric antigen receptor-engineered T (CAR-T) cells have extraordinary effect in treating lymphoblastic leukemia. However, treatment of acute myeloid leukemia (AML) using CAR-T cells remains limited to date. Leukemogenesis always relates with the abnormalities of cytogenetics, and nearly one third of AML patients have activating mutations in Fms-like tyrosine kinase 3 (FLT3) which reminded poor prognosis. Considering the FLT3 expressed in AML patients' blast cells, it may be a new candidate target for CAR-T therapy to treat FLT3+ AML, especially patients harboring FLT3-ITD mutation...
May 2, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29713515/the-role-of-tal1-in-hematopoiesis-and-leukemogenesis
#18
E R Vagapova, P V Spirin, T D Lebedev, V S Prassolov
TAL1 (SCL/TAL1, T-cell acute leukemia protein 1) is a transcription factor that is involved in the process of hematopoiesis and leukemogenesis. It participates in blood cell formation, forms mesoderm in early embryogenesis, and regulates hematopoiesis in adult organisms. TAL1 is essential in maintaining the multipotency of hematopoietic stem cells (HSC) and keeping them in quiescence (stage G0). TAL1 forms complexes with various transcription factors, regulating hematopoiesis (E2A/HEB, GATA1-3, LMO1-2, Ldb1, ETO2 , RUNX1, ERG, FLI1)...
January 2018: Acta Naturae
https://www.readbyqxmd.com/read/29706577/spred1-safeguards-hematopoietic-homeostasis-against-diet-induced-systemic-stress
#19
Yuko Tadokoro, Takayuki Hoshii, Satoshi Yamazaki, Koji Eto, Hideo Ema, Masahiko Kobayashi, Masaya Ueno, Kumiko Ohta, Yuriko Arai, Eiji Hara, Kenichi Harada, Masanobu Oshima, Hiroko Oshima, Fumio Arai, Akihiko Yoshimura, Hiromitsu Nakauchi, Atsushi Hirao
Stem cell self-renewal is critical for tissue homeostasis, and its dysregulation can lead to organ failure or tumorigenesis. While obesity can induce varied abnormalities in bone marrow components, it is unclear how diet might affect hematopoietic stem cell (HSC) self-renewal. Here, we show that Spred1, a negative regulator of RAS-MAPK signaling, safeguards HSC homeostasis in animals fed a high-fat diet (HFD). Under steady-state conditions, Spred1 negatively regulates HSC self-renewal and fitness, in part through Rho kinase activity...
April 18, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29697484/cohesin-in-haematopoiesis-and-leukaemia
#20
Roman Galeev, Jonas Larsson
PURPOSE OF REVIEW: Disturbance of the delicate balance between self-renewal and differentiation in haematopoietic stem cells (HSCs) can lead to both leukaemia and bone marrow failure. The regulation of this balance in HSC biology has been intensely investigated in several model systems, and lately the importance of epigenetic modifications as well as the organization and architecture of chromatin has become increasingly recognized. In this review, we will focus on the role of the chromatin organizing protein complex cohesin in regulation of normal and malignant haematopoiesis...
April 24, 2018: Current Opinion in Hematology
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