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Acute undifferentiated leukemia

Zixing Liu, Kelly R Smith, Hung T Khong, Jingshan Huang, Eun-Young Erin Ahn, Ming Zhou, Ming Tan
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy. Although it has been reported that overexpression of miR-125b leads to T-ALL development, the underlying mechanisms of miR-125b action are still unclear. The goal of this study is to delineate the role of miR-125b in T-ALL development. We found that miR-125b is highly expressed in undifferentiated leukemic T cells (CD4-negative) while its expression is low in differentiated T cells (CD4-positive). Overexpression of miR-125b increased the CD4-negative population in T cells, whereas depletion of miR-125b by miR-125b-sponge decreased the CD4-negative cell population...
September 14, 2016: Oncotarget
Tobias Gyárfás, Juergen Wintgens, Wolfgang Biskup, Ilske Oschlies, Wolfram Klapper, Reiner Siebert, Susanne Bens, Claudia Haferlach, Roland Meisel, Michaela Kuhlen, Arndt Borkhardt
BACKGROUND: Neonatal leukemia is a rare disease with an estimated prevalence of about one to five in a million neonates. The majority being acute myeloid leukemia (AML), neonatal leukemia can present with a variety of symptoms including hyperleucocytosis, cytopenia, hepatosplenomegaly, and skin infiltrates. Chromosomal rearrangements including mixed lineage leukemia (MLL) translocations are common in neonatal AML. CASE PRESENTATION: A female neonate born at 34 weeks gestation presented with cardiorespiratory failure, hepatosplenomegaly, pancytopenia, and coagulopathy...
December 2016: Molecular and Cellular Pediatrics
Adhra Al-Mawali, David Gillis, Ian Lewis
BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder presenting with accumulation of proliferating undifferentiated blasts. Xenograft transplantation studies have demonstrated a rare population of leukemia-initiating cells called leukemic stem cells (LSCs) capable of propagating leukemia that are enriched in the CD34+/CD38- fraction. LSCs are quiescent, resistant to chemotherapy and likely responsible for relapse and therefore represent an ideal target for effective therapy...
2016: Journal of Hematology & Oncology
Seyed Ali Nabavizadeh, Joel Stein, Suyash Mohan
Leukemias are a heterogeneous group of hematologic malignancies that results from uncontrolled neoplastic proliferation of undifferentiated or partially differentiated hematopoietic cells. Patients with acute leukemia can have a variety of craniocerebral complications, which can result from direct leukemic involvement, secondary to cerebrovascular or infectious complications of leukemia, or can be treatment related. Imaging plays a central role in evaluating the central nervous system during treatment in patients with leukemia...
August 2016: Hematology/oncology Clinics of North America
Hong-Hu Zhu, Xiao-Su Zhao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang
The SET nuclear proto-oncogene (SET)-nucleoporin (NUP)214 fusion gene, which results from cryptic t(9;9)(q34;q34) or del(9)(q34.11q34.13), is a rare genetic event in hematological malignancies. The majority of patients carrying SET-NUP214 experience T-cell acute lymphoblastic leukemia (T-ALL), but rarely experience acute undifferentiated leukemia or acute myeloid leukemia. The current study presents the case of a 19-year-old male patient with B-cell ALL (B-ALL) carrying the SET-NUP214 fusion gene, in addition to an fms-related tyrosine kinase 3-internal tandem duplication mutation and a complex karyotype abnormality...
April 2016: Oncology Letters
Veronika Polishchuk, Sajad Khazal, Giorgi Berulava, Michael Roth, Kris M Mahadeo
Patients with acute leukemias of undifferentiated lineage (AUL) generally have guarded prognosis. Here, we describe the first reported pediatric patient with AUL refractory to high-dose chemotherapy who achieved clinical remission with ALL maintenance therapy and 5-azacitidine. His induction remission was followed by consolidation with reduced toxicity haploidentical hematopoietic stem cell transplant (HSCT). At 9 months post-HSCT, the patient is alive and in remission. This combination therapy of remission induction with ALL maintenance therapy and 5-azacitidine and consolidation with reduced toxicity haploidentical HSCT is novel and promising for patients who lack conventional donors and are not candidates for myeloablative therapy...
June 2016: Pediatric Blood & Cancer
Kerstin Maria Kampa-Schittenhelm, Olaf Salitzky, Figen Akmut, Barbara Illing, Lothar Kanz, Helmut Rainer Salih, Marcus Matthias Schittenhelm
BACKGROUND: It has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity--however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia. METHODS: To test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo. Expression analysis for the CB1/2 receptors was performed by Western immunoblotting and flow cytometry...
2016: BMC Cancer
Yan-Ru Niu, Bing Wei, Bi Chen, Li-Hua Xu, Xia Jing, Cai-Ling Peng, Tian-Zhong Ma
Amodiaquine (AQ) is routinely prescribed as an anti-malarial drug. Here, we evaluated AQ-induced toxicity in the male reproductive system. Eighty adult male Sprague-Dawley rats were randomly divided into four groups that received distilled water (control) or daily doses of 5 mg/kg body weight, 10 mg/kg, or 15 mg/kg AQ for 2 weeks. Testes morphology was analyzed using hematoxylin-and-eosin staining, terminal dUTP nicked-end labeling (TUNEL), and immunostaining whereas protein expression was determined by Western blotting...
February 2016: Molecular Reproduction and Development
Rakel B Forthun, Carina Hinrichs, Tara H Dowling, Øystein Bruserud, Frode Selheim
Acute myeloid leukemia (AML) is characterized as a heterogeneous disease where the patients are sub grouped according to several classification systems and mutational analyses. Diagnosis of AML is based on identification of the specific myeloid cell initiating the disease, quantification of immature blasts in bone marrow and peripheral blood, as well as detection of mutations and translocations. The heterogeneity of AML is caused by a block in differentiation that may occur in any of the different myeloid cell populations...
2016: Current Pharmaceutical Biotechnology
Rimma Berenstein
Acute myeloid leukemia (AML) is a complex disease caused by deregulation of multiple signaling pathways. Mutations in class III receptor tyrosine kinases (RTKs) have been implicated in alteration of cell signals concerning the growth and differentiation of leukemic cells. Point mutations, insertions, or deletions of RTKs as well as chromosomal translocations induce constitutive activation of the receptor, leading to uncontrolled proliferation of undifferentiated myeloid blasts. Aberrations can occur in all domains of RTKs causing either the ligand-independent activation or mimicking the activated conformation...
2015: Biomarker Insights
Anna Porwit, Marie C Béné
OBJECTIVES: This session of the Society for Hematopathology/European Association for Haematopathology Workshop focused on acute leukemias of ambiguous origin. METHODS: We provide an overview of mixed-phenotype acute leukemia (MPAL) as recognized in the current World Health Organization classification and summarize diagnostic criteria for major categories of MPAL: B/myeloid, T/myeloid, B/T, and B/T/myeloid. RESULTS: Most MPAL cases submitted were B/myeloid and T/myeloid MPAL, the most frequent types, but three cases of B/T MPAL were also submitted, and examples of all categories are illustrated...
September 2015: American Journal of Clinical Pathology
W L Chen, D F Luo, C Gao, Y Ding, S Y Wang
The familial acute myeloid leukemia related factor gene (FAMLF) was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMCs) from 119 patients with de novo acute leukemia (AL) and 104 healthy controls, as well as in CD34+ cells from 12 AL patients and 10 healthy donors...
July 2015: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Takayuki Hoshii, Atsushi Hirao
Constitutive activation of mTOR is associated with acceleration of leukemia development. However, mTORC1 functions in established leukemia are unclear. We evaluated the role of mTORC1 in mouse acute myeloid leukemia (AML) cells using a murine model of conditional deletion of Raptor, an essential component of mTORC1, and an MLL-AF9-driven leukemia model. mTORC1 is essential for leukemia initiation, but a subset of AML cells with undifferentiated phenotypes survived long-term in the absence of mTORC1 activity...
April 2015: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Franck Morceau, Sébastien Chateauvieux, Marion Orsini, Anne Trécul, Mario Dicato, Marc Diederich
In addition to apoptosis resistance and cell proliferation capacities, the undifferentiated state also characterizes most cancer cells, especially leukemia cells. Cell differentiation is a multifaceted process that depends on complex regulatory networks that involve transcriptional, post-transcriptional and epigenetic regulation of gene expression. The time- and spatially-dependent expression of lineage-specific genes and genes that control cell growth and cell death is implicated in the process of maturation...
November 1, 2015: Biotechnology Advances
Miroslawa Siatecka, Shefali Soni, Antanas Planutis, James J Bieker
Erythroid Kruppel-like factor (EKLF or KLF1) is a transcription factor crucial for red cell development that is directly involved in regulation of a large number of erythroid genes. EKLF serves mostly as an activator of expression of these genes; however, it can act also as a repressor. Here, we present evidence that EKLF interacts with proteins from the PIAS (protein inhibitor of activated STAT) family that convey repressive activity to EKLF in the absence of sumoylation. Our studies identify PIAS3 as a transcriptional corepressor of EKLF for at least a subset of its target genes during erythropoiesis (e...
April 10, 2015: Journal of Biological Chemistry
Ariz Akhter, Jay L Patel, Fahad Farooq, Abid Qureshi, Meer-Shahbani Taher-Rad, Ghaleb Elyamany, Ali M Al-Zahrani, Fariborz Rashid-Kolvear, Adnan Mansoor
MicroRNA (MIR) signatures are critical to pathobiology and prognosis of acute myeloid leukemia (AML). MIR223 is expressed at low levels in progenitor cells, whereas high expression is induced by granulocytic differentiation. Novel-targeted therapies through epigenetic manipulation of MIR223 regulators are being explored in AML but correlative data between established clinical prognostic markers and MIR223 expression in AML is lacking. MIR223 has inverse relationship with LMO2 protein expression and our group has recently reported a close association between LMO2 protein expression and chromosomal findings in AML patients...
November 2015: Applied Immunohistochemistry & Molecular Morphology: AIMM
Preeti Ashok Dharmani, Neha Manish Mittal, P G Subramanian, Komal Galani, Yajamanam Badrinath, Pratibha Amare, Sumeet Gujral
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of acute leukemia that typically follows a highly aggressive clinical course in adults, whereas experience in children with this disease is very limited. We report cases of two children in whom bone marrow showed infiltration by large atypical monocytoid 'blast-like' cells which on immunophenotyping expressed CD4, CD56, HLA-DR and CD33 while were negative for CD34 other T-cell, B-cell and myeloid markers. The differential diagnoses considered were AML, T/NK-cell leukemia and acute undifferentiated leukemia...
January 2015: Indian Journal of Pathology & Microbiology
Xiaoqun Zheng, Yan Gao, Qi Zhang, Yanqing Liu, Ying Peng, Miao Fu, Yanhong Ji
Human cytomegalovirus (HCMV) interleukin-10 (hcmvIL-10), encoded by HCMV UL111A gene, is a homolog of human IL-10. It exerts immunomodulatory effects that allow HCMV to evade host defense mechanisms. However, the exact mechanism underlying the regulation of hcmvIL-10 expression is not well understood. The transcription factor acute myeloid leukemia 1 (AML-1) plays an important role in the regulation of various genes involved in the differentiation of hematopoietic lineages. A putative AML-1 binding site is present within the upstream regulatory region (URR) of UL111A gene...
2015: PloS One
Zohreh Sanaat, Reza Khalili, Shohreh Almasi, Mohammad Reza Aliparasti, Seyed-Mohammad Tavangar, Aliakbar Movasaghpoor, Fariba Kazemi, Arash Davani
INTRODUCTION: Acute Myeloid Leukemia is a malignant transformation of hematopoietic tissue, bone marrow infiltration of undifferentiated cells known as blasts that interfere with the production of normal cells. Vascular endothelial growth factor (VEGF) is persistently secreted from myeloid cells and high levels can be detected in patients' serum. METHODS: Twenty-one AML patients, who were chemotherapy candidates were evaluated in a clinical trial. Serum VEGF was measured by ELISA...
July 1, 2014: International Journal of Hematology-oncology and Stem Cell Research
John Fischer, Stefano Rossetti, Arani Datta, Kevin Eng, Alessandro Beghini, Nicoletta Sacchi
BACKGROUND: Core Binding Factor acute myeloid leukemia (CBF-AML) with t(8;21) RUNX1-MTG8 or inv(16) CBFB-MYH11 fusion proteins often show upregulation of wild type or mutated KIT receptor. However, also non-CBF-AML frequently displays upregulated KIT expression. In the first part of this study we show that KIT expression can be also upregulated by miR-17, a regulator of RUNX1, the gene encoding a CBF subunit. Interestingly, both CBF leukemia fusion proteins and miR-17, which targets RUNX1-3'UTR, negatively affect a common core RUNX1-miRNA mechanism that forces myeloid cells into an undifferentiated, KIT-induced, proliferating state...
2015: Molecular Cancer
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