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Acute undifferentiated leukemia

Robert E Brown, Kristine E Konopka, Priya Weerasinghe, Vanya Jaitly, Amitava Dasgupta, Mary F McGuire, Nghia D Nguyen
B-cell acute lymphoblastic leukemia (ALL) represents a malignant process in which bone marrow-derived lymphoblasts retain their undifferentiated state. Genetic testing has revealed either no identifiable cytogenetic and genomic abnormalities in such patients or a wide range of aberrations that may or may not contribute to the block in differentiation and the associated proliferation of the malignant lymphoblasts in cases of B-cell ALL. In this study, we applied morphoproteomics to a representative spectrum of cases of newly diagnosed B-cell ALL in order to identify pathways that are known to be associated with the maintenance of the undifferentiated state while promoting proliferation...
January 2017: Annals of Clinical and Laboratory Science
Amitabh Singh, Anirban Mandal, Vijay Guru, Rachna Seth
BACKGROUND: Acute lymphoblastic leukemia (ALL), the commonest malignancy of childhood, is known to manifest with a myriad of atypical presentations. Nephromegaly is a rare presentation of childhood ALL with hepatic mass being even rarer. CASE PRESENTATION: We present a 3 year-old child with unilateral renal mass and hepatic mass lesion with normal blood counts, initially suspected to have metastatic Wilms tumor based on clinical, radiological and WT1 positivity on immunocytochemistry of renal mass...
September 2016: Gulf Journal of Oncology
Takanori Fukuta, Shu Nakamoto, Yoshinori Hashimoto, Takayuki Tanaka, Yusuke Tokuyasu, Junko Maruyama, Hiromi Omura, Norihiko Hino, Satoshi Kuwamoto, Ichiro Murakami
A 75-year-old woman was referred to our hospital with suspected leukemia. Complete blood count demonstrated WBC 3,810/µl with 26% blasts, Hb of 11.7 g/dl and Plt of 18.0×10(4)/µl. Bone marrow aspiration revealed blasts (86.3%) with expressions of CD34, CD7, TdT, CD33, and CD117. MPO was negative. Chromosomal analysis of the bone marrow showed isolated trisomy 10 in all leukemic cells (20/20). Swelling of superficial lymph nodes was also observed. Cervical lymph node biopsy revealed leukemic blasts which had the same phenotype as those in the bone marrow except that proliferation of Langerhans cell-like cells (LCs) was observed in the paracortex...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
María José Torres, Angélica Fierro, C David Pessoa-Mahana, Javier Romero-Parra, Gonzalo Cabrera, Mario Faúndez
Leukotriene A4 hydrolase is a soluble enzyme with epoxide hydrolase and aminopeptidase activities catalysing the conversion of leukotriene A4 to leukotriene B4 and the hydrolysis of the peptide proline-glycine-proline. Imbalances in leukotriene B4 synthesis are related to several pathologic conditions. Currently there are no available drugs capable to modulate the synthesis of leukotriene B4 or to block its receptors. Here we show the inhibitory profile of alpha lipoic acid on the activity of leukotriene A4 Hydrolase...
January 26, 2017: European Journal of Pharmacology
Vanessa J Dayton, Robert W McKenna, Sophia L Yohe, Michelle M Dolan, Elizabeth Courville, Harold Alvarez, Michael A Linden
Objectives: Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. Methods: By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review...
January 1, 2017: American Journal of Clinical Pathology
Olga K Weinberg, Aliyah R Sohani, Parul Bhargava, Valentina Nardi
Acute myeloid leukemia (AML) is characterized by a clonal expansion of undifferentiated myeloid precursors resulting in impaired hematopoiesis and bone marrow failure. In 2016, the World Health Organization (WHO) published revisions to the classification of myeloid neoplasms and acute leukemias. Similar to the 2008 classification, the updated classification incorporates clinical features, morphology, immunophenotyping, and cytogenetics, with greater emphasis on molecular genetics, to define disease entities...
March 2017: American Journal of Hematology
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...
November 29, 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...
July 27, 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...
January 16, 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
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