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Acute lymphocytic leukemia

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https://www.readbyqxmd.com/read/28423578/endothelial-microparticles-delivering-microrna-155-into-t-lymphocytes-are-involved-in-the-initiation-of-acute-graft-versus-host-disease-following-allogeneic-hematopoietic-stem-cell-transplantation
#1
Ran Zhang, Xiaoxiao Wang, Mei Hong, Ting Luo, Miaomiao Zhao, Haorui Shen, Jun Fang, Xiaojie Li, Sibin Zang, Ping Chen, Dimin Nie, Peng Zheng, Qiuling Wu, Linghui Xia
Endothelial microparticles (EMPs) upregulation has been observed in acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the role of EMPs remains unclear. We found that EMPs derived from TNF-α-stimulated human umbilical vein endothelial cells (EA.hy926) concentrated more microRNA-155 (miR-155) compared with maternal cells. The miR-155 levels in MPs from peripheral blood of aGVHD patients and mice were remarkably elevated and significantly higher than the levels in plasma...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418653/synthesis-and-biological-evaluation-of-the-first-triple-inhibitors-of-human-topoisomerase-1-tyrosyl-dna-phosphodiesterase-1-tdp1-and-tyrosyl-dna-phosphodiesterase-2-tdp2
#2
Ping Wang, Mohamed S A Elsayed, Caroline B Plescia, Azhar Ravji, Christophe E Redon, Evgeny Kiselev, Christophe Marchand, Olga Zeleznik, Keli Agama, Yves Pommier, Mark Cushman
Tdp1 and Tdp2 are two tyrosyl-DNA phosphodiesterases that can repair damaged DNA resulting from topoisomerase inhibitors and a variety of other DNA-damaging agents. Both Tdp1 and Tdp2 inhibition could hypothetically potentiate the cytotoxicities of topoisomerase inhibitors. This study reports the successful structure-based design and synthesis of new 7-azaindenoisoquinolines that act as triple inhibitors of Top1, Tdp1, and Tdp2. Enzyme inhibitory data and cytotoxicity data from human cancer cell cultures establish that modification of the lactam side chain of the 7-azaindenoisoquinolines can modulate their inhibitory potencies and selectivities vs Top1, Tdp1, and Tdp2...
April 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28415763/low-numbers-of-pre-leukemic-fusion-genes-are-frequently-present-in-umbilical-cord-blood-without-affecting-dna-damage-response
#3
Pavol Kosik, Milan Skorvaga, Matus Durdik, Lukas Jakl, Ekaterina Nikitina, Eva Markova, Katarina Kozics, Eva Horvathova, Igor Belyaev
Despite widely accepted notion that many childhood leukemias are likely developed from hematopoietic stem/progenitor cells (HSPC) with pre-leukemic fusion genes (PFG) formed in embryonic/fetal development, the data on PFG incidence in newborns are contradictive. To provide a better understanding of a prenatal origin of leukemia, umbilical cord blood from 500 newborns was screened for the presence of the most frequent PFG associated with pediatric B-cell acute lymphoblastic leukemia. This screening revealed relatively high incidence of ETV6-RUNX1, BCR-ABL1 (p190) and MLL-AF4 at very low frequencies, averaging ~14 copies per 100,000 cells...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408486/targeting-ror1-identifies-new-treatment-strategies-in-hematological-cancers
#4
REVIEW
Hanna Karvonen, Wilhelmiina Niininen, Astrid Murumägi, Daniela Ungureanu
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28405516/assessment-of-tumor-infiltrating-tcrv%C3%AE-9v%C3%AE-2-%C3%AE-%C3%AE-lymphocyte-abundance-by-deconvolution-of-human-cancers-microarrays
#5
Marie Tosolini, Frédéric Pont, Mary Poupot, François Vergez, Marie-Laure Nicolau-Travers, David Vermijlen, Jean-Emmanuel Sarry, Francesco Dieli, Jean-Jacques Fournié
Most human blood γδ cells are cytolytic TCRVγ9Vδ2(+) lymphocytes with antitumor activity. They are currently investigated in several clinical trials of cancer immunotherapy but so far, their tumor infiltration has not been systematically explored across human cancers. Novel algorithms allowing the deconvolution of bulk tumor transcriptomes to find the relative proportions of infiltrating leucocytes, such as CIBERSORT, should be appropriate for this aim but in practice they fail to accurately recognize γδ T lymphocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28403603/b-lymphocytic-infiltration-of-the-prostate-to-a-patient-with-chronic-lymphocytic-leukemia-a-case-report
#6
Ioannis Anastasiou, Spyridon Skoufias, Ioannis Katafigiotis, Ioannis Skarmoutsos, Constantinos A Constantinides
Involvement of the prostate gland, as an early extra-nodal manifestation of a hematologic disease, or as a secondary infiltration is rare. Even rarer is the acute urinary retention due to infiltration by lymphocytes and simultaneously enlarged prostate. We present a case of a 61 years old male patient with a history of chronic lymphocytic leukemia, who was under oncological follow-up with no active treatment and had typical lower urinary tract symptoms due to benign prostatic hyperplasia and was receiving 5-alpha reductase inhibitor...
March 31, 2017: Archivio Italiano di Urologia, Andrologia
https://www.readbyqxmd.com/read/28403512/mitotic-figure-in-the-peripheral-blood-smear
#7
Sebastian Hörber, Ingo Rettig, Andreas Peter
A previously healthy 19-year-old man presented with fever, sore throat and strong feeling of illness. Physical examination showed strong swelling of throat tonsils and moderate hepatosplenomegaly. The laboratory values were as following: a total white blood count of 10.9 x 10(9) /L, hemoglobin 14.1 g/dL and a platelet count of 109 x 10(9) /L. Total bilirubin was 1.4 mg/dL and CRP was 1.32 mg/dL. The serological analyses revealed IgG and IgM antibodies against EBV-VCA consistent with an acute Epstein-Barr virus infection...
April 12, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28396161/isolated-extramedullary-relapse-of-acute-leukemia-after-allogeneic-stem-cell-transplantation-different-kinetics-and-better-prognosis-than-systemic-relapse
#8
Noga Shem-Tov, Francesco Saraceni, Ivetta Danylesko, Roni Shouval, Ronit Yerushalmi, Arnon Nagler, Avichai Shimoni
Allogeneic stem-cell transplantation (SCT) is curative treatment in patients with acute leukemia and MDS. However, recurrent disease is the major cause of treatment failure. Isolated extramedullary-relapse (iEMR) after SCT is relatively rare and not well characterized. We performed retrospective analysis of 566 consecutive patients with AML (n=446) and ALL (n=120) following SCT to study the incidence, risk factors, treatment options and outcome of iEMR. The 5-year cumulative incidence of bone-marrow relapse (BMR) and iEMR was 41...
April 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28395942/ex-vivo-t-cell-depleted-allogeneic-stem-cell-transplantation-for-hematologic-malignancies-the-search-for-an-optimum-transplant-t-cell-dose-and-t-cell-add-back-strategy
#9
Prathima Anandi, Xin Tian, Sawa Ito, Pawel Muranski, Puja D Chokshi, Noelle Watters, Upneet Chawla, Nancy Hensel, David F Stroncek, Minoo Battiwalla, A John Barrett
BACKGROUND: T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10(4)/kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10(7)/kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT...
April 7, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28390035/primary-fungal-prophylaxis-in-acute-leukemia-patients-with-different-risk-factors-retrospective-analysis-from-the-caesar-study
#10
Rongli Zhang, Jing Chen, He Huang, Jun Ma, Fanyi Meng, Yongmin Tang, Jianda Hu, Xi Zhang, Yu Ji, Huisheng Ai, Yingmin Liang, Depei Wu, Xiaojun Huang, Mingzhe Han
Invasive fungal disease (IFD) is a major cause of morbidity and mortality in acute leukemia (AL) patients. The impact of primary antifungal prophylaxis (PAP) on AL patients with different risk factors is unclear. We analyzed 2015 Chinese AL patients who received a total of 2274 chemotherapy courses, including 1410 courses in acute myeloid leukemia (AML) patients and 864 courses in acute lymphocytic leukemia (ALL) patients. The IFD incidence was significantly higher among AML than ALL patients (11.8 vs. 7.1%, P < 0...
April 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28382538/treatment-of-philadelphia-chromosome-positive-acute-lymphocytic-leukemia
#11
REVIEW
Aaron Ronson, Ariella Tvito, Jacob M Rowe
Opinion statementOver the past 15 years, the landscape of Ph+ ALL has changed dramatically. No longer the most dreaded form of acute leukemia, the advent of tyrosine kinase inhibitors (TKIs) has ushered in a new era, as TKIs have become the backbone of any treatment regimen for Ph+ ALL. A greater number achieve a complete remission allowing for more patients to get the transplant, although probably less patients need a transplant. For the first time in decades, there is hope for older patients with Ph+ ALL...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28382423/ordinary-differential-equation-models-for-adoptive-immunotherapy
#12
Anne Talkington, Claudia Dantoin, Rick Durrett
Modified T cells that have been engineered to recognize the CD19 surface marker have recently been shown to be very successful at treating acute lymphocytic leukemias. Here, we explore four previous approaches that have used ordinary differential equations to model this type of therapy, compare their properties, and modify the models to address their deficiencies. Although the four models treat the workings of the immune system in slightly different ways, they all predict that adoptive immunotherapy can be successful to move a patient from the large tumor fixed point to an equilibrium with little or no tumor...
April 5, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28379283/blinatumomab-blincyto%C3%A2-lessons-learned-from-the-bispecific-t-cell-engager-bite%C3%A2-in-acute-lymphocytic-leukemia-all
#13
Greg Friberg, David Reese
BiTE® antibody constructs are single-chain bispecific antibodies with specificity for CD3 on the T cell and a selected surface antigen on a tumor cell. When infused into patients, they are capable of eliciting a polyclonal T cell response that is unrestricted by T cell receptor specificity, presence of MHC class, or additional T cell co-stimuli. The most clinically advanced is the CD19/CD3 construct blinatumomab (Blincyto®), which is approved in the US and EU for relapsed and refractory Philadelphia negative B-cell precursor ALL...
March 31, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28377362/-promoter-methylation-and-expression-of-death-associated-protein-kinase-gene-in-acute-leukemia
#14
Wei-Hua Zhao, Fan-Yi Meng, Yong-Rong Lai, Zhi-Gang Peng, Jie Ma
OBJECTIVE: To study the clinical implications of death-associated protein kinase (DAPK) promoter methylation and DAPK gene expression in untreated patients with acute leukemia. METHODS: Methylation-specific PCR and RT-PCR were employed to detect the DAPK gene methylation and mRNA expression in the bone marrow of 60 patients with acute myeloid leukemia (AML), 55 patients with acute lymphocytic leukemia (ALL), and 17 normal subjects. RESULTS: The positivity rate of DAPK methylation was significantly higher in ALL patients (29...
March 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28372728/determination-of-cdna-encoding-bcr-abl-fusion-gene-in-patients-with-chronic-myelogenous-leukemia-using-a-novel-fret-based-quantum-dots-dna-nanosensor
#15
Mojtaba Shamsipur, Vahid Nasirian, Ali Barati, Kamran Mansouri, Asad Vaisi-Raygani, Soheila Kashanian
In the present study, we developed a sensitive method based on fluorescence resonance energy transfer (FRET) for the determination of the BCR/ABL fusion gene, which is used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). For this purpose, CdTe quantum dots (QDs) were conjugated to amino-modified 18-mer oligonucleotide ((N)DNA) to form the QDs-(N)DNA nanosensor. In the presence of methylene blue (MB) as an intercalator, the hybridization of QDs-(N)DNA with the target BCR/ABL fusion gene (complementary DNA), brings the MB (acceptor) at close proximity of the QDs (donor), leading to FRET upon photoexcitation of the QDs...
May 8, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28370903/impact-of-post-transplant-minimal-residual-disease-on-the-clinical-outcome-of-pediatric-acute-leukemia
#16
Katsutsugu Umeda, Atsushi Iwai, Koji Kawaguchi, Masamitsu Mikami, Seishiro Nodomi, Satoshi Saida, Hidefumi Hiramatsu, Toshio Heike, Katsuyuki Ohmori, Souichi Adachi
This retrospective study examined the clinical significance of FCM-MRD in 36 patients with ALL and 29 patients with AML after their first allogeneic HSCT. Hematological (FCM-MRD ≥5.0%) and molecular relapse (FCM-MRD <5.0%) were first detected in 10 and two patients with ALL and in seven and eight patients with AML, respectively. Eight of 10 patients with molecular relapse eventually progressed to hematological relapse, although most were treated with immunological intervention by aggressive discontinuation of immunosuppressive therapy or donor lymphocyte infusion...
March 31, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28369766/method-for-dna-ploidy-analysis-along-with-immunophenotyping-for-rare-populations-in-a-sample-using-fxcycle-violet
#17
Prashant Tembhare, Yajamanam Badrinath, Sitaram Ghogale, Papagudi Ganesan Subramanian
The clinical use of flow cytometric DNA ploidy assay has been extended towards stratifying the risk of diseases, such as monoclonal gammopathies or B cell acute lymphoblastic leukemia, and to detect circulating tumor cells, both of which require detection of minute cell populations. This unit describes a protocol for determining DNA ploidy in fixed samples with simultaneous surface immunophenotyping. It is an easy method for simultaneous 6- to 8-color immunophenotyping and DNA content analysis using FxCycle Violet (FCV; DAPI) dye...
April 3, 2017: Current Protocols in Cytometry
https://www.readbyqxmd.com/read/28363872/novel-therapeutic-strategies-to-target-leukemic-cells-that-hijack-compartmentalized-continuous-hematopoietic-stem-cell-niches
#18
REVIEW
Vashendriya V V Hira, Cornelis J F Van Noorden, Hetty E Carraway, Jaroslaw P Maciejewski, Remco J Molenaar
Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes...
March 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28353016/new-therapeutic-strategies-in-acute-lymphocytic-leukemia
#19
REVIEW
Louise M Man, Amy L Morris, Michael Keng
Most drugs used in standard regimens for acute lymphoblastic leukemia (ALL) were developed more than 30 years ago. Since that time, several new drugs have been developed and incorporated into ALL treatment. In spite of this, novel therapeutic approaches are still needed to improve outcomes for high-risk or relapsed ALL. This manuscript discusses newer treatment strategies, including purine nucleoside analogs, monoclonal antibodies, antibody drug conjugates, mammalian target of rapamycin (mTOR) inhibitors, proteasome inhibitors, histone deacetylase (HDAC) inhibitors, hypomethylating agents, spleen tyrosine kinase inhibitors, Bruton's tyrosine kinase (BTK) inhibitors, Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors, anti-programmed cell death protein (anti-PD-1) antibodies, mitogen-activated protein kinase (MEK) inhibitors, CXCR4 antagonists, poly (ADP-ribose) polymerase (PARP) inhibitors, and FMS-like tyrosine kinase 3 (FLT3) inhibitors...
March 28, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28350342/the-role-of-pi3k-isoforms-in-regulating-bone-marrow-microenvironment-signaling-focusing-on-acute-myeloid-leukemia-and-multiple-myeloma
#20
REVIEW
Rachel E Piddock, Kristian M Bowles, Stuart A Rushworth
Despite the development of novel treatments in the past 15 years, many blood cancers still remain ultimately fatal and difficult to treat, particularly acute myeloid leukaemia (AML) and multiple myeloma (MM). While significant progress has been made characterising small-scale genetic mutations and larger-scale chromosomal translocations that contribute to the development of various blood cancers, less is understood about the complex microenvironment of the bone marrow (BM), which is known to be a key player in the pathogenesis of chronic lymphocytic leukaemia (CLL), AML and MM...
March 28, 2017: Cancers
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