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Acute lymphoid leukemia

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https://www.readbyqxmd.com/read/29044676/world-health-organization-defined-eosinophilic-disorders-2017-update-on-diagnosis-risk-stratification-and-management
#1
Jason Gotlib
DISEASE OVERVIEW: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. DIAGNOSIS: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm(3) and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder...
November 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29038614/dna-methylation-events-as-markers-for-diagnosis-and-management-of-acute-myeloid-leukemia-and-myelodysplastic-syndrome
#2
REVIEW
Geórgia Muccillo Dexheimer, Jayse Alves, Laura Reckziegel, Gabrielle Lazzaretti, Ana Lucia Abujamra
During the onset and progression of hematological malignancies, many changes occur in cellular epigenome, such as hypo- or hypermethylation of CpG islands in promoter regions. DNA methylation is an epigenetic modification that regulates gene expression and is a key event for tumorigenesis. The continuous search for biomarkers that signal early disease, indicate prognosis, and act as therapeutic targets has led to studies investigating the role of DNA in cancer onset and progression. This review focuses on DNA methylation changes as potential biomarkers for diagnosis, prognosis, response to treatment, and early toxicity in acute myeloid leukemia and myelodysplastic syndrome...
2017: Disease Markers
https://www.readbyqxmd.com/read/29032268/total-marrow-lymphoid-irradiation-fludarabine-melphalan-tfm-conditioning-for-allogeneic-hematopoietic-cell-transplantation-hct
#3
Lindsay G Jensen, Tracey Stiller, Jeffrey Y C Wong, Joycelynne Palmer, Anthony Stein, Joseph Rosenthal
BACKGROUND: Reduced intensity conditioning regimens (RIC) for hematopoietic stem cell transplantation (HCT) can reduce morbidity and mortality, but patients with advanced disease may require alternate approaches. In an initial report of RIC (Fludarabine (FLU) and Melphalan (MEL)) with total-marrow-lymphoid irradiation (TMLI) in HCT for advanced hematological malignancies in 33 patients, we found the addition of TMLI to RIC was feasible and safe. Here we report long-term outcomes for these patients...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29032147/high-bone-marrow-mir-19b-level-predicts-poor-prognosis-and-disease-recurrence-in-de-novo-acute-myeloid-leukemia
#4
Ting-Juan Zhang, Jiang Lin, Jing-Dong Zhou, Xi-Xi Li, Wei Zhang, Hong Guo, Zi-Jun Xu, Yang Yan, Ji-Chun Ma, Jun Qian
Oncogenic role of miR-19 family has been identified in human cancers especially in lymphoid malignancies. However, to date, little studies investigated the role of miR-19 family in myeloid malignancies. Herein, we examined miR-19a/b expression and explored its clinical significance in de novo acute myeloid leukemia (AML). The detection of miR-19a/b expression was performed by real-time quantitative PCR in bone marrow mononuclear cells of 113 patients and 42 healthy donors. Both miR-19a/b levels were significantly increased in AML patients in contrast to controls...
October 12, 2017: Gene
https://www.readbyqxmd.com/read/29025601/a-neoplasm-with-fip1l1-pdgfra-fusion-presenting-as-pediatric-t-cell-lymphoblastic-leukemia-lymphoma-without-eosinophilia
#5
Matthew J Oberley, Christopher Denton, Jianling Ji, Matthew Hiemenz, Deepa Bhojwani, Dejerianne Ostrow, Samuel Wu, Paul Gaynon, Gordana Raca
The 2016 World Health Organization (2016 WHO) classification of hematopoietic malignancies classifies neoplasms with a fusion between the FIP1L1 and PDGFRA genes in 4q12 into a group called "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2". Neoplasms characterized by this fusion are pluripotent stem cell disorders that can show both myeloid and lymphoid differentiation. They typically occur in adult patients and most are characterized by eosinophilia...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28978828/familial-hematological-malignancies
#6
Shinsuke Hirabayashi, Atsushi Manabe
The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. The study of cancer genomes has identified inherited genetic drivers that predispose cancer cells to clonal evolution. The revisions in the categories of myeloid neoplasms and acute leukemia were published as a monograph in 2016. We described familial hematological malignancies using the 2016 edition of the WHO classification.
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978065/the-pan-bcl-2-blocker-obatoclax-gx15-070-and-the-pi3-kinase-mtor-inhibitor-bez235-produce-cooperative-growth-inhibitory-effects-in-all-cells
#7
Gabriele Stefanzl, Daniela Berger, Sabine Cerny-Reiterer, Katharina Blatt, Gregor Eisenwort, Wolfgang R Sperr, Gregor Hoermann, Karin Lind, Alexander W Hauswirth, Peter Bettelheim, Heinz Sill, Junia V Melo, Ulrich Jäger, Peter Valent
Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the regulation of growth and survival of ALL cells. We examined the effects of the pan-BCL-2 blocker obatoclax and the PI3-kinase/mTOR-inhibitor BEZ235 on growth and survival of ALL cells...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977998/nkl-homeobox-gene-msx1-acts-like-a-tumor-suppressor-in-nk-cell-leukemia
#8
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
NKL homeobox gene MSX1 is physiologically expressed in lymphoid progenitors and subsequently downregulated in developing T- and B-cells. In contrast, elevated expression levels of MSX1 persist in mature natural killer (NK)-cells, indicating a functional role in this compartment. While T-cell acute lymphoblastic leukemia (T-ALL) subsets exhibit aberrant overexpression of MSX1, we show here that in malignant NK-cells the level of MSX1 transcripts is aberrantly downregulated. Chromosomal deletions at 4p16 hosting the MSX1 locus have been described in NK-cell leukemia patients...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28943878/triplebody-mediates-increased-anti-leukemic-reactivity-of-il-2-activated-donor-natural-killer-nk-cells-and-impairs-viability-of-their-cd33-expressing-nk-subset
#9
Stephan Kloess, Alessa Ede Valverde da Silva, Olaf Oberschmidt, Tanja Gardlowski, Nadine Matthies, Maulik Vyas, Lubomir Arseniev, Michael Heuser, Elke Pogge von Strandmann, Ulrike Köhl
Natural killer cells (NK) are essential for the elimination of resistant acute myeloid and acute lymphoblastic leukemia (AML and ALL) cells. NK cell-based immunotherapies have already successfully entered for clinical trials, but limitations due to immune escape mechanisms were identified. Therefore, we extended our established NK cell protocol by integration of the previously investigated powerful trispecific immunoligand ULBP2-aCD19-aCD33 [the so-called triplebodies (TBs)] to improve the anti-leukemic specificity of activated NK cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28934678/establishment-of-cell-line-with-nk-nkt-phenotype-from-myeloid-nk-cell-acute-leukemia
#10
A Darji, N Desai, R Modi, B Khamar, S Rajkumar
Acute Myeloid Leukemia (AML) is the most common malignancy in adults with a 5-year survival rate of 27% of the total affected population. For effective treatment and new drug discovery, cell lines are considered as a very important tool. Here we report an establishment of a continuous human cell line AML-004 with a hypo-diploid chromosome 44 and presence of both NK/NKT phenotypes. The cell line was isolated from the blood sample of myeloid NK cell acute leukemia patients and extensively characterized by flow cytometery, morphology, and cytogentic analysis...
October 2017: Leukemia Research
https://www.readbyqxmd.com/read/28927157/selected-mirna-levels-are-associated-with-ikzf1-microdeletions-in-pediatric-acute-lymphoblastic-leukemia
#11
J Krzanowski, J Madzio, A Pastorczak, A Tracz, M Braun, J Tabarkiewicz, A Pluta, W Młynarski, I Zawlik
The clinical outcome of children with high-risk relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is poor. The present study assessed the utility and prognostic value of selected microRNA (miRNA/miR) in BCP-ALL. The changes in the expression levels of these miRNAs regarding known gene lesions affecting lymphoid development [early B-cell factor 1 (EBF1), ETS variant 6 (ETV6), IKAROS family zinc finger 1 (IKZF1), paired box 5 (PAX5), cyclin dependent kinase inhibitor (CDKN) 2A/CDKN2B, retinoblastoma 1 (RB1), pseudoautosomal region 1 (PAR1), B-cell translocation gene 1 protein (BTG1)] were analyzed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28903943/therapeutic-potential-of-sgn-cd19b-a-pbd-based-anti-cd19-drug-conjugate-for-treatment-of-b-cell-malignancies
#12
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
#13
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
#14
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
#15
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
#16
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
#17
Norio Asou, Hiroyuki Fujita, Katsuji Shinagawa
No abstract text is available yet for this article.
October 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28853417/recommendations-for-cerebrospinal-fluid-examination-in-acute-leukemia
#18
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
#19
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...
November 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
#20
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
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