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Acute lymphocytic leukemia

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https://www.readbyqxmd.com/read/29333004/drosha-rs642321-polymorphism-influence-susceptibility-to-childhood-acute-lymphoblastic-leukemia-a-preliminary-report
#1
Mohammad Hashemi, Seyed-Shahaboddin Hasani, Majid Naderi
Introduction: It has been well known that the microRNA biogenesis is involved in the pathogenesis of various diseases. We investigated the possible association between DROSHA rs642321 variant and risk of acute lymphocytic leukemia (ALL). Materials and Methods: We genotyped 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group) by the tetra amplification refractory mutation system-polymerase chain reaction...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29330145/mbd2-ablation-impairs-lymphopoiesis-and-impedes-progression-and-maintenance-of-t-all
#2
Mi Zhou, Kuangguo Zhou, Ling Cheng, Xing Chen, Jue Wang, Xiao-Min Wang, Yingchi Zhang, Qilin Yu, Shu Zhang, Di Wang, Liang Huang, Mei Huang, Ding Ma, Tao Cheng, Cong-Yi Wang, Weiping Yuan, Jianfeng Zhou
Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29324279/inhibition-of-udp-glucose-dehydrogenase-by-6-thiopurine-and-its-oxidative-metabolites-possible-mechanism-for-its-interaction-within-the-bilirubin-excretion-pathway-and-6tp-associated-liver-toxicity
#3
Chamitha J Weeramange, Cassie M Binns, Chixiang Chen, Ryan J Rafferty
6-Thiopurine (6TP) is an actively prescribed drug in the treatment of various diseases ranging from Crohn's disease and other inflammatory diseases to acute lymphocytic leukemia and non-Hodgkin's leukemia. While 6TP has beneficial therapeutic uses, severe toxicities are also reported with its use, such as jaundice and liver toxicity. While numerous investigations into the mode in which toxicity originates has been undertaken. None have investigated the effects of inhibition towards UDP-Glucose Dehydrogenase (UDPGDH), an oxidative enzyme responsible for UDP-glucuronic acid (UDPGA) formation or UDP-Glucuronosyl transferase (UGT1A1), which is responsible for the conjugation of bilirubin with UDPGA for excretion...
December 30, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29323085/cd19-negative-b-lineage-acute-lymphoblastic-leukemia-a-diagnostic-and-therapeutic-challenge
#4
Shashi Bansal, Upendra Sharma, Akansha Jain, Richa Sharma, Bhargav Yagnik
B-lineage acute lymphoblastic leukemia (B-ALL) is an aggressive neoplasm of B-lymphocyte precursors that express the pan B-cell marker CD19 in all the cases. Rarely, a case may be assigned as B-lineage even if CD19 is negative. Here, a 16-year-old male presented with complaints of pain abdomen, on and off fever, joint pain, and hepatosplenomegaly for 2 months. Bone marrow examination was suggestive of acute leukemia with numerous leukoblasts on aspiration. On flow cytometry, gated blast population was negative for CD19, cytoCD3, and myeloperoxidase MPO and positive for CD34, TdT, HLA-DR, CD22, CD79a, and CD10...
October 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29322435/vaccine-associated-paralytic-poliomyelitis-in-a-patient-with-acute-lymphocytic-leukemia
#5
Reza Taherkhani, Fatemeh Farshadpour, Mohammad Reza Ravanbod
We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in an immunocompromised patient with acute lymphocytic leukemia who was initially diagnosed with aseptic meningitis. Isolation of Sabin-like type 1 poliovirus from the patient's cerebrospinal fluid made this a case of vaccine-related poliovirus (VRPV) infection. The patient developed paralysis and respiratory distress and deceased a few months after onset of paralysis with respiratory failure. This tragic case report highlights the emergence of VAPP and indicates the importance of timely diagnosis of VRPV infections to improve clinical management of VRPV-infected patients and to prevent the devastating consequences of silent introduction of VRPVs in treatment wards and eventually in the society...
January 10, 2018: Journal of Neurovirology
https://www.readbyqxmd.com/read/29321210/the-immune-checkpoint-modulator-ox40-and-its-ligand-ox40l-in-nk-cell-immunosurveillance-and-acute-myeloid-leukemia
#6
Tina Nuebling, Carla Emilia Schumacher, Martin Hofmann, Ilona Hagelstein, Benjamin Joachim Schmiedel, Stefanie Maurer, Birgit Federmann, Kathrin Rothfelder, Malte Roerden, Daniela Dorfel, Pascal Schneider, Gundram Jung, Helmut Rainer Salih
The TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint to reinforce antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte subset that contributes to antitumor immunity, particularly in leukemia. Accordingly, these cells are being clinically evaluated for cancer treatment through multiple approaches, such as adoptive transfer of ex vivo expanded polyclonal NK cells (pNKC). Here we analyzed whether and how OX40 and its ligand (OX40L) influence NK-cell function and anti-leukemia reactivity...
January 10, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29320898/did-i-miss-it-discovering-hidden-coexisting-hematological-neoplasms-a-single-institutional-review-of-100-collision-tumors
#7
Evan Himchak, Etan Marks, Yang Shi, Yanhua Wang
A collision tumor is defined as two histologically distinct tumor types identified at the same anatomic site. Hematolymphoid proliferative disorders (HLPDs), which coincide with non-hematological neoplasms, can mimic an immune response and can easily be overlooked as an immune reaction to a solid organ neoplasm, especially when low grade. In order to avoid a delay in the diagnosis of a HLPD during the workup for a non-hematological neoplasm, we identified a cohort of 100 cases with a HLPD diagnosis during the initial workup and treatment of a non-hematological neoplasm, or vice versa...
January 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29313067/combinatorial-effects-of-histone-deacetylase-inhibitors-hdaci-vorinostat-and-entinostat-and-adaphostin-are-characterized-by-distinct-redox-alterations
#8
Nilsa Rivera-Del Valle, Tiewei Cheng, Mary E Irwin, Hayley Donnella, Melissa M Singh, Joya Chandra
PURPOSE: Amongst the epigenetically targeted therapies, targeting of the histone deacetylases (HDACs) has yielded numerous drugs for clinical use in hematological malignancies, but none as yet for acute lymphocytic leukemia (ALL). Single agent activity of HDAC inhibitors (HDACi) has been elusive in ALL, and has prompted study of combinatorial strategies. Because several HDACi raise levels of intracellular oxidative stress, we evaluated combinations of two structurally distinct HDACi with the redox active compound adaphostin in ALL...
January 8, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29310835/april-gene-expression-in-a-cohort-of-egyptian-acute-myeloid-leukemia-patients-clinical-and-prognostic-significance
#9
Amira Ahmed Hammam, Shereen Mohamed Elhoseiny, Rania El-Sayed Sheir, Hisham Issa
APRIL (A Proliferation Inducing Ligand) is a member of the tumor necrosis factor (TNF) family. It is essential for the survival of normal and malignant B lymphocytes. Increased expression of APRIL is noted in most of hematological malignancies and auto immune diseases. We investigated the expression level of APRIL mRNA in 50 de novo acute myeloid leukemia (AML) patients, together with 20 healthy controls using a Real-Time Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RTQ-PCR) with a specific aim of determining its relation to clinical features and laboratory findings at diagnosis and its impact on the response to therapy...
January 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29304116/the-sorafenib-anti-relapse-effect-after-allohsct-is-associated-with-heightened-alloreactivity-and-accumulation-of-cd8-pd-1-cd279-lymphocytes-in-marrow
#10
Andrzej Lange, Emilia Jaskula, Janusz Lange, Grzegorz Dworacki, Dorota Nowak, Aleksandra Simiczyjew, Monika Mordak-Domagala, Mariola Sedzimirska
We studied three FLT3 ITD acute myeloid leukemia (AML) patients who relapsed after allogeneic haematopoietic stem cell transplantation (alloHSCT) and received multikinase inhibitor (MKI) sorafenib as part of salvage therapy. MKI was given to block the effect of FLT3 ITD mutation which powers proliferation of blast cells. However, the known facts that sorafenib is more effective in patents post alloHSCT suggested that this MKI can augment the immune system surveillance on leukaemia. In the present study, we investigated in depth the effect of sorafenib on the alloreactivity seen post-transplant including that on leukaemia...
2018: PloS One
https://www.readbyqxmd.com/read/29296896/maintenance-of-telomere-length-in-aml
#11
REVIEW
Peter M Lansdorp
The importance of telomere length to human health, aging, and cancer continues to be underappreciated. This review examines some basics of telomere biology and relates how telomere function, telomerase activity, and mutations in TERC or TERT are involved in bone marrow failure, leukemias, and other cancers. Given the challenge to obtain accurate data on telomerase activity and telomere length in specific cell types, the situation in acute myeloid leukemia (AML) remains puzzling. In most cancers, telomerase levels are increased after cells have encountered a "telomere crisis," which is typically associated with poor prognosis...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296885/blockade-of-cd7-expression-in-t-cells-for-effective-chimeric-antigen-receptor-targeting-of-t-cell-malignancies
#12
Yi Tian Png, Natasha Vinanica, Takahiro Kamiya, Noriko Shimasaki, Elaine Coustan-Smith, Dario Campana
Effective immunotherapies for T-cell malignancies are lacking. We devised a novel approach based on chimeric antigen receptor (CAR)-redirected T lymphocytes. We selected CD7 as a target because of its consistent expression in T-cell acute lymphoblastic leukemia (T-ALL), including the most aggressive subtype, early T-cell precursor (ETP)-ALL. In 49 diagnostic T-ALL samples (including 14 ETP-ALL samples), median CD7 expression was >99%; CD7 expression remained high at relapse (n = 14), and during chemotherapy (n = 54)...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296850/progressive-multifocal-leukoencephalopathy-and-hematologic-malignancies-a-single-cancer-center-retrospective-review
#13
Elizabeth C Neil, Lisa M DeAngelis
Progressive multifocal leukoencephalopathy (PML) is an uncommon opportunistic infection with high morbidity and mortality. This is an institutional review board-approved retrospective review of medical records identified by diagnostic coding for PML or John Cunningham virus (JCV) from 2000 to 2015. Inclusion criteria were cerebrospinal fluid (CSF) positive for JCV by polymerase chain reaction or brain biopsy-proven PML in non-HIV patients. There were 16 patients, 12 of whom were men (75%); the median age was 56 years (range, 31-71 years)...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296821/progenitor-b-1-b-cell-acute-lymphoblastic-leukemia-is-associated-with-collaborative-mutations-in-3-critical-pathways
#14
Sheryl M Gough, Liat Goldberg, Marbin Pineda, Robert L Walker, Yuelin J Zhu, Sven Bilke, Yang Jo Chung, Joseph Dufraine, Subhadip Kundu, Elad Jacoby, Terry J Fry, Susanna Fischer, Renate Panzer-Grümayer, Paul S Meltzer, Peter D Aplan
B-1 and B-2 lymphocytes are derived from distinct developmental pathways and represent layered arms of the innate and adaptive immune systems, respectively. In contrast to a majority of murine B-cell malignancies, which stain positive with the B220 antibody, we discovered a novel form of B-cell leukemia in NUP98-PHF23 (NP23) transgenic mice. The immunophenotype (Lin- B220- CD19+ AA4.1+) was identical to that of progenitor (pro) B-1 cells, and VH gene usage was skewed toward 3' V regions, similar to murine fetal liver B cells...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29279551/unilateral-conjunctival-infiltration-of-adult-t-cell-leukemia-lymphoma-case-report-and-literature-review
#15
Joji Shimono, Shigeki Kaino, Kohei Okada, Kazuo Oshimi, Yusuke Ishida, Tatsuro Takahashi, Takuto Miyagishima, Takanori Teshima
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by human T-cell leukemia virus type 1 infection. Although conjunctival lymphoma is commonly reported with B-cell lymphoma, it rarely occurs in cases of ATLL. A 73-year-old Japanese female patient was admitted to our institution with evidence of abnormal lymphocytes, lymphadenopathy, and lung nodular lesions. Acute type ATLL was diagnosed, and therapy following the mLSG15 protocol was initiated. At the end of the second course, new bone lesions were detected...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29275177/synergistic-therapeutic-effect-of-diethylstilbestrol-and-cx-4945-in-human-acute-t-lymphocytic-leukemia-cells
#16
Jung-Il Jung, Kyeong-Yong Park, Soon Ae Kim, Jiyeon Kim
Human acute T-lymphocytic leukemia (T-ALL) is one of the most commonly diagnosed hematological disorders, and is characterized by poor prognosis and survival rate. Despite the development of new therapeutic approaches, leukemia treatment options remain limited. In this study, we investigated the immunosuppressive and anti-proliferative effects of the synthetic estrogen diethylstilbestrol (DES), both alone and combined with the casein kinase 2 (CK2) inhibitor CX-4945. Our results indicated that DES induced caspase-dependent apoptosis in a human T-ALL cell line (Jurkat cells), while exerting no significant cytotoxicity in normal peripheral blood mononuclear cells (PBMCs)...
December 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29273895/smear-campaign-misattribution-of-pancytopenia-to-a-tick-borne-illness
#17
Jessica Lee, Soraya Azzawi, Michael J Peluso, Aaron Richterman, Haiyan Ramirez Batlle, Maria A Yialamas
We report the case of a 51-year-old woman presenting with a targetoid rash and pancytopenia after a tick bite. Initial evaluation was notable for severe neutropenia on the complete blood cell count differential, a positive Lyme IgM antibody, and a peripheral blood smear demonstrating atypical lymphocytes. While her pancytopenia was initially attributed to tick-borne illness, peripheral flow cytometry showed 7% myeloblasts, and a bone marrow biopsy confirmed 60% blasts. The patient was ultimately diagnosed with acute myelogenous leukemia, in addition to early, localized Lyme disease...
December 22, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29249175/a-tool-compound-targeting-the-core-binding-factor-runt-domain-to-disrupt-binding-to-cbf%C3%AE-in-leukemic-cells
#18
Zaw Min Oo, Anuradha Illendula, Jolanta Grembecka, Charles Schmidt, Yunpeng Zhou, Virginie Esain, Wanda Kwan, Isaura Frost, Trista E North, Roger A Rajewski, Nancy A Speck, John H Bushweller
The core binding factor (CBF) gene RUNX1 is a target of chromosomal translocations in leukemia, including t(8;21) in acute myeloid leukemia (AML). Normal CBF function is essential for activity of AML1-ETO, product of the t(8;21), and for survival of several leukemias lacking RUNX1 mutations. Using virtual screening and optimization, we developed Runt domain inhibitors which bind to the Runt domain and disrupt its interaction with CBFβ. On-target activity was demonstrated by the Runt domain inhibitors' ability to depress hematopoietic cell formation in zebrafish embryos, reduce growth and induce apoptosis of t(8;21) AML cell lines, and reduce progenitor activity of mouse and human leukemia cells harboring the t(8;21), but not normal bone marrow cells...
December 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29245929/harnessing-the-heart-s-resistance-to-malignant-tumors-cardiac-derived-extracellular-vesicles-decrease-fibrosarcoma-growth-and-leukemia-related-mortality-in-rodents
#19
Lilian Grigorian-Shamagian, Soraya Fereydooni, Weixin Liu, Antonio Echavez, Eduardo Marbán
The heart is known for its resistance to cancer. Although different conjectures have been proposed to explain this phenomenon, none has been tested. We propose that the heart microenvironment may exert anti-cancer properties. So, our objective was to test the anti-oncogenic potential of cardiac-derived extracellular vesicles (EVs). For that EVs secreted by cardiosphere-derived cells (CDCs, heart progenitor cells) were tested in vitro on fibrosarcoma HT1080. In vivo models comprised the xenograft HT1080 fibrosarcoma in athymic mice (n=35), and spontaneous acute lymphocyte leukemia in old rats (n=44)...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29244249/flow-cytometric-false-myeloperoxidase-positive-childhood-b-lineage-acute-lymphoblastic-leukemia
#20
Süreyya Savaşan, Steven Buck, Manisha Gadgeel, Ali Gabali
BACKGROUND: Flow cytometric intracellular myeloperoxidase (MPO) staining of leukemic blasts is a useful tool in diagnosis of leukemia subtype. Interpretation of high MPO-positivity can be a diagnostic challenge in B-lineage acute lymphoblastic leukemia (B-ALL). While very few such cases have been reported, high MPO positive B-ALL cases without additional myeloid antigen positivity are suspect and require further investigation. METHODS: Three pediatric cases of B-ALL with strong MPO staining (clone 8E6; Invitrogen) at diagnosis and three others with negative MPO staining were studied by flow cytometry and immunohistochemistry...
December 15, 2017: Cytometry. Part B, Clinical Cytometry
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