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Leukemia Research and Treatment

Patience Uchenna Tweteise, Bernard Natukunda, Joel Bazira
Background. The human T-cell lymphotropic virus types 1 and 2 (HTLV 1/2) are retroviruses associated with different pathologies. HTLV-1 causes adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP); HTLV-2 is not clearly associated with a known clinical disease. Both viruses may be transmitted by whole blood transfusion, from mother to child predominantly through breastfeeding, and by sexual contact. Presently, none of the regional blood banks in Uganda perform routine pretransfusion screening for HTLV...
2016: Leukemia Research and Treatment
Ursula Rochau, Martina Kluibenschaedl, David Stenehjem, Kuo Kuan-Ling, Jerald Radich, Gary Oderda, Diana Brixner, Uwe Siebert
Currently several tyrosine kinase inhibitors (TKIs) are approved for treatment of chronic myeloid leukemia (CML). Our goal was to identify the optimal sequential treatment strategy in terms of effectiveness and cost-effectiveness for CML patients within the US health care context. We evaluated 18 treatment strategies regarding survival, quality-adjusted survival, and costs. For model parameters, the literature data, expert surveys, registry data, and economic databases were used. Evaluated strategies included imatinib, dasatinib, nilotinib, bosutinib, ponatinib, stem-cell transplantation (SCT), and chemotherapy...
2015: Leukemia Research and Treatment
Kalubai Vari Khajapeer, Rajasekaran Baskaran
Chronic myeloid leukemia (CML) is a hematological malignancy that arises due to reciprocal translocation of 3' sequences from c-Abelson (ABL) protooncogene of chromosome 9 with 5' sequence of truncated break point cluster region (BCR) on chromosome 22. BCR-ABL is a functional oncoprotein p210 that exhibits constitutively activated tyrosine kinase causing genomic alteration of hematopoietic stem cells. BCR-ABL specific tyrosine kinase inhibitors (TKIs) successfully block CML progression. However, drug resistance owing to BCR-ABL mutations and overexpression is still an issue...
2015: Leukemia Research and Treatment
Eyad Alhourani, Martina Rincic, Joana B Melo, Isabel M Carreira, Anita Glaser, Beate Pohle, Cordula Schlie, Thomas Liehr
In chronic lymphocytic leukemia (CLL), presence of acquired cytogenetic abnormalities may help to estimate prognosis. However, deletion of TP53 gene, which is associated with an aggressive course of the disease and poor prognosis along with a lack of response to treatment, is one of the alterations which may escape cytogenetic diagnoses in CLL. Thus, other techniques have emerged such as interphase fluorescence in situ hybridization (iFISH). Deletion of TP53 may but must not go together with the formation of an isochromosome i(17q); surprisingly this subgroup of patients was not in the focus of CLL studies yet...
2015: Leukemia Research and Treatment
A Rodríguez-Lirio, G Pérez-Yarza, M R Fernández-Suárez, E Alonso-Tejerina, M D Boyano, A Asumendi
Recent epidemiological studies indicate that the antidiabetic drug metformin has chemosensitizing and chemopreventive effects against carcinogenesis. Here, we demonstrate that metformin exerts varying degrees of antitumor activity against human leukemia cells, as reflected by differences in growth inhibition, apoptosis, and alterations to metabolic enzymes. In metformin-sensitive cells, autophagy was not induced but rather it blocked proliferation by means of arresting cells in the S and G2/M phases which was associated with the downregulation of cyclin A, cyclin B1, and cdc2, but not that of cyclin E...
2015: Leukemia Research and Treatment
Plumelle Yves, Michel Stephane, Banydeen Rishika, Delaunay Christine, Panelatti Gérard
We describe the clinical and biological features of ten patients with a survival superior to ten years (long survival), out of 175 patients diagnosed with Adult T-cell Leukemia/Lymphoma (ATL) in Martinique (1983-2013). There were 5 lymphoma and 5 chronic subtypes. Five of them (3 chronic, 2 lymphoma) had been treated with valproic acid (VA) for neurological disorders developed before or after ATL diagnosis, suggesting a beneficial role for VA as a histone deacetylase inhibitor (HDI) in ATL treatment. Total duration of uninterrupted VA treatment ranged from 8 to 37 years...
2015: Leukemia Research and Treatment
Moneeb A K Othman, Martina Rincic, Joana B Melo, Isabel M Carreira, Eyad Alhourani, Friederike Hunstig, Anita Glaser, Thomas Liehr
Acute leukemia often presents with pure chromosomal resolution; thus, aberrations may not be detected by banding cytogenetics. Here, a case of 26-year-old male diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and a normal karyotype after standard GTG-banding was studied retrospectively in detail by molecular cytogenetic and molecular approaches. Besides fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and high resolution array-comparative genomic hybridization (aCGH) were applied...
2014: Leukemia Research and Treatment
Susumu Inoue, Isra'a Khan, Rao Mushtaq, Dawn Carson, Elna Saah, Nkechi Onwuzurike
Children with AML become profoundly neutropenic while they undergo remission induction chemotherapy. It is unknown whether these children should be kept in the hospital while they are severely neutropenic to prevent life-threatening complications associated with neutropenia and reduce fatality. We at our institution routinely discharge patients after completing remission induction chemotherapy in the presence of profound neutropenia, unless it is clinically contraindicated. We reviewed all AML patients who were consecutively treated at our hospital from 1989 to 2011...
2014: Leukemia Research and Treatment
Pilar de la Puente, Barbara Muz, Feda Azab, Micah Luderer, Abdel Kareem Azab
Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients will eventually relapse or become refractory to the treatments. Although the treatments have improved, the major problem in MM is the resistance to therapy. Novel agents are currently in development for the treatment of relapsed/refractory MM, including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, cell signaling targeted therapies, and strategies targeting the tumor microenvironment. We have previously reviewed in detail the contemporary immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies therapies for MM...
2014: Leukemia Research and Treatment
Merav Bar, Brent L Wood, Jerald P Radich, Kristine C Doney, Ann E Woolfrey, Colleen Delaney, Frederick R Appelbaum, Ted A Gooley
In this retrospective study, we evaluated the impact of pre- and posttransplant minimal residual disease (MRD) detected by multiparametric flow cytometry (MFC) on outcome in 160 patients with ALL who underwent myeloablative allogeneic hematopoietic cell transplantation (HCT). MRD was defined as detection of abnormal B or T cells by MFC with no evidence of leukemia by morphology (<5% blasts in marrow) and no evidence of extramedullary disease. Among 153 patients who had pre-HCT flow data within 50 days before transplant, MRD pre-HCT increased the risk of relapse (hazard ratio (HR) = 3...
2014: Leukemia Research and Treatment
Hilde Kvestad, Lasse Evensen, James B Lorens, Oystein Bruserud, Kimberley J Hatfield
The combined use of the histone deacetylase inhibitor valproic acid (VPA), the retinoic acid receptor- α agonist all-trans retinoic acid (ATRA), and the deoxyribonucleic acid polymerase- α inhibitor cytarabine (Ara-C) is now considered for disease-stabilizing treatment of acute myeloid leukemia (AML). Leukemogenesis and leukemia cell chemoresistance seem to be supported by neighbouring stromal cells in the bone marrow, and we have therefore investigated the effects of these drugs on primary human endothelial cells and the osteoblastic Cal72 cell line...
2014: Leukemia Research and Treatment
Hiroko Fukushima, Takashi Fukushima, Aiko Sakai, Ryoko Suzuki, Ryoko Nakajima-Yamaguchi, Chie Kobayashi, Atsushi Iwabuchi, Makoto Saito, Ai Yoshimi, Tomohei Nakao, Keisuke Kato, Masahiro Tsuchida, Hideto Takahashi, Kazutoshi Koike, Nobutaka Kiyokawa, Emiko Noguchi, Ryo Sumazaki
Backgrounds. Outcome of childhood malignancy has been improved mostly due to the advances in diagnostic techniques and treatment strategies. While methotrexate (MTX) related polymorphisms have been under investigation in childhood malignancies, many controversial results have been offered. Objectives. To evaluate associations of polymorphisms related MTX metabolisms and clinical course in childhood lymphoid malignancies. Method. Eighty-two acute lymphoblastic leukemia and 21 non-Hodgkin's lymphoma children were enrolled in this study...
2013: Leukemia Research and Treatment
Jolly Patel, Melissa Ho, Viet Ho, Celeste Bello, Benjamin Djulbegovic, Lubomir Sokol, Gene Wetzstein
Rituximab is an anti-CD-20 monoclonal antibody used in the management of lymphoproliferative disorders. The use of maintenance rituximab has improved progression free survival and overall survival in follicular lymphomas. Although rapid rituximab infusions have been studied extensively, there is little data on the use of rapid infusions during maintenance therapy for low grade lymphomas. The primary objective of this retrospective analysis was to evaluate the incidence of Grade 3 and 4 toxicities with maintenance rapid infusion rituximab according to the Common Terminology Criteria for Adverse Events version 4 (CTC v...
2013: Leukemia Research and Treatment
Marilyn Wright, Angie Bryans, Kaylin Gray, Leah Skinner, Amanda Verhoeve
The purpose of this study was to examine physical activity levels and influencing individual and environmental factors in a group of adolescent survivors of cancer and a comparison group. Methods. The study was conducted using a "mixed methods" design. Quantitative data was collected from 48 adolescent survivors of cancer and 48 comparison adolescents using the Godin Leisure-Time Exercise Questionnaire, the Fatigue Scale-Adolescents, and the Amherst Health and Activity Study-Student Survey. Qualitative data was collected in individual semistructured interviews...
2013: Leukemia Research and Treatment
Ugo Testa, Elvira Pelosi
The development of the genetic studies on acute myeloid leukemias (AMLs) has led to the identification of some recurrent genetic abnormalities. Their discovery was of fundamental importance not only for a better understanding of the molecular pathogenesis of AMLs, but also for the identification of new therapeutic targets. In this context, it is essential to identify AML-associated "driver" mutations, which have a causative role in leukemogenesis. Evidences accumulated during the last years indicate that activating internal tandem duplication mutations in FLT3 (FLT3-ITD), detected in about 20% of AMLs, represents driver mutations and valid therapeutic targets in AMLs...
2013: Leukemia Research and Treatment
Chiara Sarlo, Francesco Buccisano, Luca Maurillo, Mariagiovanna Cefalo, Luigi Di Caprio, Laura Cicconi, Concetta Ditto, Licia Ottaviani, Ambra Di Veroli, Maria Ilaria Del Principe, Maria Assunta Grasso, Daniela Nasso, Giovanna De Santis, Sergio Amadori, Adriano Venditti
We explored the safety and efficacy of bortezomib given as single agent in patients with untreated or relapsed/refractory acute myeloid leukemia (AML), unfit for conventional chemotherapy. Fourteen patients were treated with bortezomib 1.5 mg/m(2) administered twice weekly for two weeks, every 3 weeks. Median age was 70 years (range 60-81) and the median number of cycles delivered was 2 (range 1-4). Of 13 evaluable patients, in 8 (61%), the administration of bortezomib resulted in an antileukemic effect as demonstrated by peripheral blood and/or bone marrow blast reduction...
2013: Leukemia Research and Treatment
Sarah Huet, Laurent Jallades, Carole Charlot, Kaddour Chabane, Franck E Nicolini, Mauricette Michallet, Jean-Pierre Magaud, Sandrine Hayette
Somatic mutations in the NPM1 gene, which encodes for nucleophosmin, have been reported to be the most frequent genetic abnormalities found in acute myeloid leukaemia (AML). Their identification and quantification remain crucial for the patients' residual disease monitoring. We investigated a new method that could represent a novel reliable alternative to sequencing for its identification. This method was based on high-resolution melting analysis in order to detect mutated patients and on an allele-specific oligonucleotide real-time quantitative polymerase chain reaction (ASO-RQ-PCR) for the identification and quantification of the transcripts carrying NPM1 mutations (NPM1m)...
2013: Leukemia Research and Treatment
Gabriela Nestal de Moraes, Paloma Silva Souza, Fernanda Casal de Faria Costas, Flavia Cunha Vasconcelos, Flaviana Ruade Souza Reis, Raquel Ciuvalschi Maia
Chronic myeloid leukemia (CML) is a clonal hematopoietic disorder characterized by the presence of the Philadelphia chromosome which resulted from the reciprocal translocation between chromosomes 9 and 22. The pathogenesis of CML involves the constitutive activation of the BCR-ABL tyrosine kinase, which governs malignant disease by activating multiple signal transduction pathways. The BCR-ABL kinase inhibitor, imatinib, is the front-line treatment for CML, but the emergence of imatinib resistance and other tyrosine kinase inhibitors (TKIs) has called attention for additional resistance mechanisms and has led to the search for alternative drug treatments...
2012: Leukemia Research and Treatment
Yao Yuan, Siddha Kasar, Chingiz Underbayev, Sindhuri Prakash, Elizabeth Raveche
Common blood disorders include hematopoietic cell malignancies or leukemias and plasma cell dyscrasia, all of which have associated microRNA abnormalities. In this paper, we discuss several leukemias including acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) and identify altered microRNAs and their targets. Immune disorders with altered blood levels of antibodies include autoimmune disorders, such as systemic lupus erythematosus (SLE) with associated anti-self-autoantibodies and immunoglobulin A nephropathy (IgAN) also have related microRNA abnormalities...
2012: Leukemia Research and Treatment
Bulent Ozpolat, Ugur Akar, Ibrahim Tekedereli, S Neslihan Alpay, Magaly Barria, Baki Gezgen, Nianxiang Zhang, Kevin Coombes, Steve Kornblau, Gabriel Lopez-Berestein
Translation initiation and activity of eukaryotic initiation factor-alpha (eIF2α), the rate-limiting step of translation initiation, is often overactivated in malignant cells. Here, we investigated the regulation and role of eIF2α in acute promyelocytic (APL) and acute myeloid leukemia (AML) cells in response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), the front-line therapies in APL. ATRA and ATO induce Ser-51 phosphorylation (inactivation) of eIF2α, through the induction of protein kinase C delta (PKCδ) and PKR, but not other eIF2α kinases, such as GCN2 and PERK in APL (NB4) and AML cells (HL60, U937, and THP-1)...
2012: Leukemia Research and Treatment
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