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Acute lymphoide leukemia

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https://www.readbyqxmd.com/read/28903943/therapeutic-potential-of-sgn-cd19b-a-pbd-based-anti-cd19-drug-conjugate-for-treatment-of-b-cell-malignancies
#1
Maureen C Ryan, Maria Corinna Palanca-Wessels, Brian Schimpf, Kristine A Gordon, Heather Kostner, Brad Meyer, Changpu Yu, Heather Van Epps, Dennis Benjamin
Patients with relapsed/refractory B-cell malignancies such as non-Hodgkin lymphoma (B-NHL) or acute lymphoblastic leukemia (B-ALL) have a poor prognosis. Despite measurable clinical activity with new targeted therapies, many patients do not achieve a complete or durable response suggesting an opportunity to improve upon existing therapies. Here we describe SGN-CD19B, a pyrrolobenzodiazepine (PBD)-based anti-CD19 antibody drug conjugate (ADC) being investigated for treatment of B-cell malignancies, which has improved potency compared to other ADCs...
September 13, 2017: Blood
https://www.readbyqxmd.com/read/28882084/genomic-characterization-of-chromosome-translocations-in-patients-with-t-myeloid-mixed-phenotype-acute-leukemia
#2
Aparna Pallavajjala, Daehwan Kim, Tongbin Li, Gabriel Ghiaur, Richard J Jones, Kathleen H Burns, Steven L Salzberg, Yi Ning
Mixed-phenotype acute leukemia (MPAL) is a progenitor type of leukemia with ambiguous expression of lineage markers. The diagnosis of MPAL is based on flow cytometric analysis of immunophenotype, which commonly identifies myeloid lineage markers as well as B- or T- lymphoid lineage markers on leukemic blasts. Due to the rare occurrence of this disease, few studies have delineated the molecular bases of MPAL. Combining conventional karyotyping with whole genomic sequencing (WGS) and RNA sequencing (RNA-seq), we report here our identification and characterization of chromosome translocations, gene mutations and gene expression profile in four patients with T/Myeloid MPAL, including two t(6;14)(q25;q32) one t(8;14)(q24...
September 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28881484/primary-cells-in-bcr-fgfr1-positive-8p11-myeloproliferative-syndrome-are-sensitive-to-dovitinib-ponatinib-and-dasatinib
#3
Niklas Landberg, Arta Dreimane, Marianne Rissler, Rolf Billström, Helena Ågerstam
OBJECTIVES: Translocations involving the Fibroblast growth factor receptor 1 (FGFR1) gene are associated with the 8p11 myeloproliferative syndrome (EMS), a rare neoplasm that following a usually short chronic phase progresses into acute myeloid or lymphoid leukemia. The treatment commonly involves chemotherapy and, if possible, allogeneic stem cell transplantation which is the only therapeutic option for long term survival. Given the aggressive course of EMS, we here evaluated tyrosine kinase inhibitors as treatment options to delay disease progression...
September 7, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28871936/xanthoma-like-skin-changes-in-an-elderly-woman-with-a-normal-lipid-profile
#4
Piotr Nockowski, Zdzisław Woźniak, Adam Reich, Joanna Maj
Dear Editor, An 83-year-old woman developed yellow-brownish infiltrates, nodules, and tumors mimicking xanthomas, mostly involving the periorbital and chest area within three months (Figure 1). She had no abnormalities in serum cholesterol or triglycerides levels. A detailed laboratory analysis revealed the presence of mild monoclonal gammopathy with a presence of immunoglobulin G (IgG) kappa light chains; however, according to hematologist consultation, it did not require medical intervention. Imaging assessment and ultrasound examination did not show any specific involvement of internal organs...
July 2017: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28860956/diagnosis-of-lymphoid-malignancy-by-pcr-for-analysis-of-antigen-receptor-rearrangement-after-blood-transfusion-in-a-dog-with-acute-lymphocytic-leukemia
#5
Suhee Kim, Hyunwoo Kim, Soo-Hyeon Lee, Ilhan Cho, Seongwoo Kang, Junwoo Bae, Woosun Kim, Soomin Ahn, Jihye Choi, Sang-Ki Kim, Yoonjung Do, Jae Gyu Yoo, Jinho Park, DoHyeon Yu
Acute lymphocytic leukemia (ALL) is uncommon lymphoid malignancy in dogs, and its diagnosis is challenging. A 14-year-old spayed female mixed breed dog was transferred to a veterinary medical teaching hospital for an immediate blood transfusion. The dog showed lethargy, pale mucous membranes, and a weak femoral pulse. Complete blood count revealed non-regenerative anemia and severe leukopenia with thrombocytopenia. ALL was tentatively diagnosed based on the predominance of immature lymphoblasts on blood film examination...
August 2017: Immune Network
https://www.readbyqxmd.com/read/28856623/jsh-guideline-for-tumors-of-hematopoietic-and-lymphoid-tissues-leukemia-2-acute-promyelocytic-leukemia-apl
#6
Norio Asou, Hiroyuki Fujita, Katsuji Shinagawa
No abstract text is available yet for this article.
August 30, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28853417/recommendations-for-cerebrospinal-fluid-examination-in-acute-leukemia
#7
Sandrine Girard, Odile Fenneteau, Fanélie Mestrallet, Xavier Troussard, Jean-François Lesesve
Cytological identification of blasts in cerebrospinal fluid in acute leukemia, lymphoid or myeloid, in adult and child, at diagnosis or during follow up lead to the diagnosis of leukemic meningitidis. Suitable CNS therapy based on a defined "CNS status" following an international standardized classification, lead to decrease cerebrospinal relapses. Established in 1993, this classification allows to treat patients based on their CNS status. Based on the red blood cells count, nucleated cells count and presence of blasts, it requires a standard technical procedure that guarantees the comparability of results coming from different medical laboratory...
August 30, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28841588/thrombosis-in-adult-patients-with-acute-leukemia
#8
Maria Ilaria Del Principe, Domenico Del Principe, Adriano Venditti
PURPOSE OF REVIEW: Recent studies indicate that the risk of thrombosis in hematologic patients may be similar or even higher than that found in patients with solid tumors. However, available information about pathogenesis and incidence of thrombosis in acute leukemia is limited. This review focuses on mechanisms underlying thrombosis in acute leukemia and discusses recent literature data. RECENT FINDINGS: In the last few years, proofs have been provided that leukemic cells release free prothrombotic products, such as micro-vesicles, tissue factors, circulating free DNA and RNA...
August 24, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28835438/molecular-synergy-underlies-the-co-occurrence-patterns-and-phenotype-of-npm1-mutant-acute-myeloid-leukemia
#9
Oliver M Dovey, Jonathan L Cooper, Annalisa Mupo, Carolyn S Grove, Claire Lynn, Nathalie Conte, Robert M Andrews, Suruchi Pacharne, Konstantinos Tzelepis, M S Vijayabaskar, Paul Green, Roland Rad, Mark Arends, Penny Wright, Kosuke Yusa, Allan Bradley, Ignacio Varela, George S Vassiliou
NPM1 mutations define the commonest subgroup of acute myeloid leukemia (AML) and frequently co-occur with FLT3 internal tandem duplications (ITD) or, less commonly, NRAS or KRAS mutations. Co-occurrence of mutant NPM1 with FLT3-ITD carries a significantly worse prognosis than NPM1-RAS combinations. To understand the molecular basis of these observations we compare the effects of the two combinations on hematopoiesis and leukemogenesis in knock-in mice. Early effects of these mutations on hematopoiesis show that compound Npm1(cA/+);Nras(G12D/+) or Npm1(cA);Flt3(ITD) share a number of features: Hox gene over-expression, enhanced self-renewal, expansion of hematopoietic progenitors and myeloid differentiation bias...
August 23, 2017: Blood
https://www.readbyqxmd.com/read/28821995/expression-of-the-pol-gene-of-human-endogenous-retroviruses-herv-k-and-w-in-leukemia-patients
#10
Massimiliano Bergallo, Paola Montanari, Katia Mareschi, Chiara Merlino, Massimo Berger, Ilaria Bini, Valentina Daprà, Ilaria Galliano, Franca Fagioli
The human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that integrated into the germ cell DNA of primates over 30 million years ago. HERV expression seems impaired in several diseases, ranging from autoimmune to neoplastic disorders. The purpose of this study was to evaluate the overall endogenous retroviral transcription profile in bone marrow (BM) samples. A total of 30 paediatric high-risk leukaemia patients (lymphoid and myeloid malignancies) were tested for HERVs virus gene expression...
August 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28804122/shp2-is-required-for-bcr-abl1-induced-hematologic-neoplasia
#11
S Gu, A Sayad, G Chan, W Yang, Z Lu, C Virtanen, R A Van Etten, B G Neel
BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph(+)) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph(+) B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation models for CML and BCR-ABL1(+) B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia...
August 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28797620/extended-follow-up-of-patients-treated-with-bendamustine-for-lymphoid-malignancies
#12
Mara Penne, Maryam Sarraf Yazdy, Kruti Sheth Nair, Bruce D Cheson
INTRODUCTION: Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments. PATIENTS AND METHODS: Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR])...
June 30, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28792162/immunological-subtypes-of-acute-lymphoblastic-leukemia-beyond-morphology-experience-from-kidwai-state-cancer-institute-bengaluru-india
#13
Namrata N Rajkumar, Raghavendra H Vijay
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is disease of lymphoid precursors and is the most common cancer. Diagnosis of ALL is made by evaluating morphology and flowcytometric Immunophenotyping (FCI)and is an important adjunct in diagnosis and determining treatment in ALL, with availability of extensive monoclonal antibodies in the recent years there is tremendous progress in the field of FCI, and is a requirement by World Health Organisation for the classification of acute lymphoblastic Leukemia...
July 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28765326/outcome-of-azacitidine-therapy-in-acute-myeloid-leukemia-is-not-improved-by-concurrent-vorinostat-therapy-but-is-predicted-by-a-diagnostic-molecular-signature
#14
Charles Craddock, Aimee E Houlton, Lynn S Quek, Paul Ferguson, Emmanouela Gbandi, Corran Roberts, Marlen Metzner, Natalia Garcia-Martin, Alison Kennedy, Angela Hamblin, Manoj Raghavan, Sandeep Nagra, Louise Dudley, Keith Wheatley, Mary Frances McMullin, Srinivas Pillai, Richard J Kelly, Shamyla Siddique, Michael Dennis, Jamie D Cavenagh, Paresh Vyas
Purpose: Azacitidine (AZA) is a novel therapeutic option in older patients with acute myeloid leukemia (AML) but its rational utilization is compromised by the fact that neither the determinants of clinical response nor its mechanism of action are defined. Co-administration of histone deacetylase inhibitors, such as vorinostat (VOR), is reported to improve the clinical activity of AZA but this has not been prospectively studied in AML. Experimental Design: We compared outcomes in 259 adults with AML (n=217) and MDS (n=42) randomized to receive either AZA monotherapy (75 mg/m(2) × seven days every 28 days) or AZA combined with VOR 300 mg bd on days 3-9 po...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28751190/septin-6-regulates-engraftment-and-lymphoid-differentiation-potential-of-murine-long-term-hematopoietic-stem-cells
#15
Katharina Senger, Gina Marka, Karin Soller, Vadim Sakk, Maria Carolina Florian, Hartmut Geiger
Septins are a family of filament-forming GTP-binding proteins that serve as scaffolds and diffusion barriers in various cellular processes. Septin 6 is known as a fusion partner of mixed-lineage leukemia in infant acute myeloid leukemia. The occurrence of the fusion gene is associated with a reduced expression of septin 6 itself. The role of septin 6 in hematopoiesis and whether it is involved in scaffolds within hematopoietic cells is not known. Septin 6-deficient hematopoietic stem cells (HSCs) present with an increased engraftment potential but altered lymphoid differentiation with a reduced contribution to the T-cell compartment and an increased B-cell contribution...
July 24, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28750861/the-tim-3-galectin-9-secretory-pathway-is-involved-in-the-immune-escape-of-human-acute-myeloid-leukemia-cells
#16
Isabel Gonçalves Silva, Inna M Yasinska, Svetlana S Sakhnevych, Walter Fiedler, Jasmin Wellbrock, Marco Bardelli, Luca Varani, Rohanah Hussain, Giuliano Siligardi, Giacomo Ceccone, Steffen M Berger, Yuri A Ushkaryov, Bernhard F Gibbs, Elizaveta Fasler-Kan, Vadim V Sumbayev
Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased translation and exocytosis of the immune receptor Tim-3 and its ligand galectin-9. This occurs in a protein kinase C and mTOR (mammalian target of rapamycin)-dependent manner...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28748759/targeting-kinase-activating-genetic-lesions-to-improve-therapy-of-pediatric-acute-lymphoblastic-leukemia
#17
Franca Raffaella, Natasa Karas Kuzelicki, Claudio Sorio, Eleonora Toffoletti, Oksana Montecchini, Alice Poropat, Marco Rabusin, Debora Curci, Dino Paladin, Gabriele Stocco, Giuliana Decorti
Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, characterized by an abnormal proliferation of immature lymphoid cells. Thanks to risk-adapted combination chemotherapy treatments currently used, survival at 5 years has reached 90%. ALL is a heterogeneous disease from a genetic point of view: patients' lymphoblasts may harbor in fact several chromosomal alterations, some of which have prognostic and therapeutic value. Of particular importance is the translocation t(9;22)(q34;q11...
July 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28740405/novel-agents-for-the-treatment-of-childhood-leukemia-an-update
#18
REVIEW
Ertugrul Eryılmaz, Cengiz Canpolat
Achieving lower morbidity and higher survival rates in the treatment of childhood leukemia has been a paradigm of success in modern oncology. However, serious long-term health complications occur in very large populations of childhood leukemia survivors, in the case of both acute lymphoid leukemia and acute myeloid leukemia (AML). Additionally, 15% of acute lymphoid leukemia patients have treatment failures, and rates are even higher in childhood AML. In the last few decades, as a result of well-tested experiments that statistically analyzed treatment cohorts, new agents have emerged as alternatives or supplements to established treatments, in which high survival and/or less morbidity were observed...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28735479/immunohistochemistry-in-acute-myeloid-leukemia
#19
Michael W Cruise
The World Health Organization's Classification of Tumours of Haematopoietic and Lymphoid Tissues (Swerdlow et al. (eds) WHO Classification of tumours of haematopoietic and lymphoid tissues, 4th edn. WHO Press, Lyon, 2008) created a classification scheme incorporating genetic, molecular, morphologic, and immunophenotypic characteristics. The diagnosis of acute myeloid leukemia requires equal to or greater than 20% blasts (except in some cases with specific cytogenetic abnormalities or in erythroleukemia). The diagnostic work up typically includes morphologic, cytochemical, and immunophenotypic features...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28735478/cytochemical-staining
#20
Michele E Paessler, Marybeth Helfrich, Gerald B W Wertheim
Historically, the diagnosis and classification of acute leukemia involved morphologic review of blasts in the peripheral blood and bone marrow smears and cytochemical staining. Cytochemical stains, which are enzymatic colorimetric reactions that occur in the cells of interest, were necessary to assign and confirm myeloid and lymphoid lineage. In the current WHO 2008 Classification of leukemia, immunophenotyping and cytogenetic analysis have largely replaced cytochemical staining in the characterization of acute leukemias...
2017: Methods in Molecular Biology
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