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acute lymphoblastic leukemia -L3 type

Noelle V Frey, David L Porter
Chimeric antigen receptors (CARs) are engineered molecules that can be introduced into T cells to enable them to target specific tumor antigens. CAR T cells targeting CD19 have shown promise in patients with relapsed and refractory B-cell neoplasms, including those with acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphomas. Notably, durable responses have been observed in patients who had not undergone consolidative stem cell transplant, a finding that correlates with reports of T-cell persistence and B-cell aplasia in studies of anti-CD19 treatment in vivo...
October 15, 2016: Oncology (Williston Park, NY)
Leylagul Kaynar, Koray Demir, Esra Ermiş Turak, Çiğdem Pala Öztürk, Gökmen Zararsız, Zeynep Burçin Gönen, Selma Gökahmetoğlu, Serdar Şıvgın, Bülent Eser, Yavuz Köker, Musa Solmaz, Ali Ünal, Mustafa Çetin
INTRODUCTION: The use of αβ+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. PATIENT AND METHOD: Thirty-four patients with acute leukemia and lacking a match donor were treated with αβ T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia...
October 10, 2016: Hematology (Amsterdam, Netherlands)
Ankur Jain, Alka Khadwal, Gaurav Prakash, Nalini Gupta, Subhash Varma, Pankaj Malhotra
Testicular involvement in a case of acute lymphoblastic leukemia (ALL) is well reported, but occurrence of "isolated" malignant hydrocele is extremely uncommon. We herein report a case of a 22-year-old man who presented to our hematology clinic with fever and easy fatiguability of 2 weeks' duration. Examination revealed pallor, cervical lymphadenopathy, and bilateral scrotal swellings. He was diagnosed as a case of Philadelphia-positive ALL (B-cell type) based on peripheral smear, bone marrow examination, and flow cytometry of the marrow aspirate...
2016: Clinical Medicine Insights. Pathology
Isabel de de la Fuente Garcia, Léna Coïc, Jean-Marie Leclerc, Caroline Laverdière, Céline Rousseau, Philippe Ovetchkine, Bruce Tapiéro
BACKGROUND: The objective of this retrospective study was to assess protection against vaccine preventable diseases (VPDs) in children treated for acute lymphoblastic leukemia (ALL). PROCEDURE: Clinical characteristics and vaccination records were collected. Antibodies against VPDs were measured after completion of chemotherapy and after a booster dose of vaccine. Immunization status of household members was evaluated. RESULTS: Sixty children were included...
October 8, 2016: Pediatric Blood & Cancer
Mareike Doerrenberg, Andreas Kloetgen, Kebria Hezaveh, Wilhelm Wössmann, Kirsten Bleckmann, Martin Stanulla, Martin Schrappe, Alice C McHardy, Arndt Borkhardt, Jessica I Hoell
For reasons not yet understood, nearly all infants with acute lymphoblastic leukemia (ALL) are diagnosed with the B-cell type, with T-ALL in infancy representing a very rare exception. Clinical and molecular knowledge about infant T-ALL is still nearly completely lacking and it is also still unclear whether it represents a distinct disease compared to childhood T-ALL. To address this, we performed exome sequencing of three infant cases, which enabled the detection of mutations in NOTCH2, NOTCH3, PTEN, and KRAS...
September 26, 2016: Genes, Chromosomes & Cancer
Daniele Kazue Sugioka, Carlos Eduardo Ibaldo Gonçalves, Maria da Graça Bicalho
BACKGROUND: Since the discovery of specific histocompatibility, literature has associated genes involved in the immune response, like the Human Leucocyte Antigen (HLA), with a better prognosis in transplantation. However, other non-HLA genes may also influence the immune process, such as the genes encoding the immunoglobulin-like receptors of natural killer cells (KIRs). The discovery that NK cell KIR receptors interact with conservative epitopes (C1, C2, Bw4) presented in HLA class I molecules that are genetically polymorphic, also observed in KIR genes, led to the investigation of the relevance of the KIR system to hematopoietic stem cell transplant...
2016: BMC Hematology
Sebastian Giebel, Myriam Labopin, Gerard Socie', Dietrich Beelen, Paul Browne, Liisa Volin, Slawomira Kyrcz-Krzemien, Ibrahim Yakoub-Agha, Mahmoud Aljurf, Depei Wu, Mauricette Michallet, Renate Arnold, Mohamad Mohty, Arnon Nagler
Allogeneic hematopoietic cell transplantation is widely used to treat adults with high risk acute lymphoblastic leukemia. The aim of this study was to analyze whether the results changed over time and to identify prognostic factors. Adult patients treated between year 1993 and 2012 with myeloablative allogeneic hematopoietic cell transplantation from HLA matched sibling (n=2681) or unrelated donors (n=2178) in first complete remission were included. For transplantations from sibling donors performed between 2008-2012, the following two-year probabilities of the overall survival were obtained: 76% (18-25 years old group), 69% (26-35 and 36-45 years old groups) and 60% (46-55 years old group)...
September 29, 2016: Haematologica
Youssef M Mosaad, Rasha Elashery, Ahmad Darwish, Omar A Sharaf Eldein, Tarek Barakat, Samy Marouf, Noha T Abou El-Khier, Laila F Youssef, Iman M Fawzy
To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = ...
August 9, 2016: Leukemia & Lymphoma
Lingbao Gao, Keyu Yuan, Wei Ding, Mei Lin
Notch signaling is a well-conserved cell-fate determining factor in embryo development, and the dyregulation of this signaling is frequently observed in many types of cancers, including hematological malignancies. In this review, we briefly describe the Notch signaling pathway, and we primarily focus on the relationship between Notch and hematological malignancies. We also discuss the clinical development of promising agents including γ-secretase inhibitors (GSIs) and monoclonal antibodies (mAbs). Complete response has been observed among patients with T-cell acute lymphoblastic leukemia (T-ALL) when treated with GSIs...
2016: Critical Reviews in Eukaryotic Gene Expression
Kristina Karrman, Bertil Johansson
The most common pediatric malignancy is acute lymphoblastic leukemia (ALL), of which T-cell ALL (T-ALL) comprises 10-15% of cases. T-ALL arises in the thymus from an immature thymocyte as a consequence of a stepwise accumulation of genetic and epigenetic aberrations. Crucial biological processes such as differentiation, self-renewal capacity, proliferation, and apoptosis are targeted and deranged by several types of neoplasia-associated genetic alteration, for example translocations, deletions, and mutations of genes that code for proteins involved in signaling transduction, epigenetic regulation, and transcription...
September 16, 2016: Genes, Chromosomes & Cancer
Shinsuke Hirabayashi, Kentaro Ohki, Kazuhiko Nakabayashi, Hitoshi Ichikawa, Yukihide Momozawa, Kohji Okamura, Akinori Yaguchi, Kazuki Terada, Yuya Saito, Ai Yoshimi, Hiroko Ogata-Kawata, Hiromi Sakamoto, Motohiro Kato, Junya Fujimura, Moeko Hino, Akitoshi Kinoshita, Hiromi Kakuda, Hidemitsu Kurosawa, Keisuke Kato, Ryosuke Kajiwara, Koichi Moriwaki, Tsuyoshi Morimoto, Kozue Nakamura, Yasushi Noguchi, Tomoo Osumi, Kazuo Sakashita, Junko Takita, Yuki Yuza, Koich Matsuda, Teruhiko Yoshida, Kenji Matsumoto, Kenichiro Hata, Michiaki Kubo, Yoichi Matsubara, Takashi Fukushima, Katsuyoshi Koh, Atsushi Manabe, Akira Ohara, Nobutaka Kiyokawa
Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 6 fusion partners have reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or PCR. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2...
September 15, 2016: Haematologica
Oxana Dobrovinskaya, Georgina Valencia-Cruz, Luis Castro-Sánchez, Edgar O Bonales-Alatorre, Liliana Liñan-Rico, Igor Pottosin
Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells...
2016: Frontiers in Pharmacology
Guillermo José Ruiz-Delgado, Yahveth Cantero-Fortiz, Andrés Aurelio León-Peña, Mónica León-González, Ana Karen Nuñez-Cortés, Guillermo José Ruiz-Argüelles
BACKGROUND: In B-cell acute lymphoblastic leukemia, one of the most frequent cytogenetic alterations is the presence of the Philadelphia chromosome. Recently, newly identified genetic alterations have been studied, among them the IKZF1 deletion. IKZF1 encodes IKAROS, a zinc finger protein that plays an important role in hematopoiesis involving the regulation process of adhesion, cellular migration, and as a tumor suppressor. OBJECTIVE: We aimed to study the impact of IKAROS deletion in the evolution and prognosis of B-cell acute lymphoblastic leukemia...
July 2016: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
Susanna Teppo, Saara Laukkanen, Thomas Liuksiala, Jessica Nordlund, Mikko Oittinen, Kaisa Teittinen, Toni Grönroos, Pascal St-Onge, Daniel Sinnett, Ann-Christine Syvänen, Matti Nykter, Keijo Viiri, Merja Heinäniemi, Olli Lohi
Approximately 20%-25% of childhood acute lymphoblastic leukemias carry the ETV6-RUNX1 (E/R) fusion gene, a fusion of two central hematopoietic transcription factors, ETV6 (TEL) and RUNX1 (AML1). Despite its prevalence, the exact genomic targets of E/R have remained elusive. We evaluated gene loci and enhancers targeted by E/R genome-wide in precursor B acute leukemia cells using global run-on sequencing (GRO-seq). We show that expression of the E/R fusion leads to widespread repression of RUNX1 motif-containing enhancers at its target gene loci...
September 12, 2016: Genome Research
Walid Sabri Hamadou, Sawsen Besbes, Violaine Bourdon, Yosra Ben Youssef, Mohamed Adnène Laatiri, Testsuro Noguchi, Abderrahim Khélif, Hagay Sobol, Zohra Soua
Mutations are responsible for familial cancer syndromes which account for approximately 5-10 % of all types of cancers. Familial cancers are often caused by genetic alterations occurring either in tumor suppressor or genomic stability genes such as TP53. In this study, we have analyzed the TP53 gene by direct sequencing approach, in a panel of 18 Tunisian familial hematological malignancies cases including several forms of leukemia, lymphoma and myeloid syndrome and 22 cases of sporadic acute leukemia. In one familial case diagnosed with acute lymphoblastic leukemia, we reported an intronic substitution 559+1 G>A which may disrupt the splice site and impact the normal protein function...
September 12, 2016: Familial Cancer
Katsuya Yamamoto, Shinichiro Kawamoto, Yu Mizutani, Kimikazu Yakushijin, Tomoe Yamashita, Yuji Nakamachi, Seiji Kawano, Yoshitake Hayashi, Hiroshi Matsuoka, Hironobu Minami
The t(12;17)(p13;q11∼21) translocation is a very rare but recurrent cytogenetic aberration observed predominantly in early pre-B acute lymphoblastic leukemia (ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand, der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation leading to trisomy 1q in myeloid malignancies. We describe here the first case of mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384, which also had der(1;18)(q10;q10) as an additional abnormality...
September 9, 2016: Cytogenetic and Genome Research
Mohammad Ali Fahmidehkar, Sayed Mohammad Shafiee, Ebrahim Eftekhar, Laleh Mahbudi, Atefeh Seghatoleslam
Ubiquitination is an important cellular mechanism with a pivotal role in the degradation of abnormal or short-lived proteins and the regulation of cell cycle and cell growth. The ubiquitin-proteasome pathway is altered in multiple types of human malignancies, including colorectal cancer (CRC). The alteration in the expression of the novel human gene ubiquitin-conjugating enzyme E2 Q1 (UBE2Q1), as a putative member of the E2 ubiquitin-conjugating enzyme family, has been reported in several malignancies, including carcinoma of the breast, hepatocellular and colorectal cancer, and pediatric acute lymphoblastic leukemia...
September 2016: Oncology Letters
Jonathan Bond, Renae Domaschenz, Mónica Roman-Trufero, Pierangela Sabbattini, Isabel Ferreiros-Vidal, Gareth Gerrard, Vahid Asnafi, Elizabeth Macintyre, Matthias Merkenschlager, Niall Dillon
Ikaros and Foxp1 are transcription factors that play key roles in normal lymphopoiesis and lymphoid malignancies. We describe a novel physical and functional interaction between the proteins, which requires the central zinc finger domain of Ikaros. The Ikaros-Foxp1 interaction is abolished by deletion of this region, which corresponds to the IK6 isoform that is commonly associated with high-risk acute lymphoblastic leukemia (ALL). We also identify the Gpr132 gene, which encodes the orphan G protein-coupled receptor G2A, as a novel target for Foxp1...
August 30, 2016: Oncotarget
Rui D Mendes, Kirsten Canté-Barrett, Rob Pieters, Jules P P Meijerink
The tumor suppressor phosphatase and tensin homolog (PTEN) negatively regulates phosphatidylinositol 3-kinase (PI3K)-AKT signaling and is often inactivated by mutations (including deletions) in a variety of cancer types, including T-cell acute lymphoblastic leukemia. Here we review mutation-associated mechanisms that inactivate PTEN together with other molecular mechanisms that activate AKT and contribute to T-cell leukemogenesis. In addition, we discuss how Pten mutations in mouse models affect the efficacy of gamma-secretase inhibitors to block NOTCH1 signaling through activation of AKT...
September 2016: Haematologica
Nathalie K Zgheib, Reem Akika, Rami Mahfouz, Carol Al Aridi, Khaled M Ghanem, Raya Saab, Miguel R Abboud, Nidale Tarek, Hassan El Solh, Samar A Muwakkit
BACKGROUND: Interindividual variability in thiopurine-related toxicity could not be completely explained by thiopurine S-methyltransferase (TPMT) polymorphisms, as a number of patients who are homozygous wild type or normal for TPMT still develop toxicity that necessitates 6-mercaptopurine (MP) dose reduction or protocol interruption. Recently, few studies reported on an inherited nucleoside diphosphate-linked moiety X motif 15 (NUDT15) c.415C>T low-function variant that is associated with decreased thiopurine metabolism and leukopenia in childhood acute lymphoblastic leukemia (ALL) and other diseases...
August 31, 2016: Pediatric Blood & Cancer
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