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Pediatric leukemias

Jinghui Zhang, Kelly McCastlain, Hiroki Yoshihara, Beisi Xu, Yunchao Chang, Michelle L Churchman, Gang Wu, Yongjin Li, Lei Wei, Ilaria Iacobucci, Yu Liu, Chunxu Qu, Ji Wen, Michael Edmonson, Debbie Payne-Turner, Kerstin B Kaufmann, Shin-Ichiro Takayanagi, Erno Wienholds, Esmé Waanders, Panagiotis Ntziachristos, Sofia Bakogianni, Jingjing Wang, Iannis Aifantis, Kathryn G Roberts, Jing Ma, Guangchun Song, John Easton, Heather L Mulder, Xiang Chen, Scott Newman, Xiaotu Ma, Michael Rusch, Pankaj Gupta, Kristy Boggs, Bhavin Vadodaria, James Dalton, Yanling Liu, Marcus L Valentine, Li Ding, Charles Lu, Robert S Fulton, Lucinda Fulton, Yashodhan Tabib, Kerri Ochoa, Meenakshi Devidas, Deqing Pei, Cheng Cheng, Jun Yang, William E Evans, Mary V Relling, Ching-Hon Pui, Sima Jeha, Richard C Harvey, I-Ming L Chen, Cheryl L Willman, Guido Marcucci, Clara D Bloomfield, Jessica Kohlschmidt, Krzysztof Mrózek, Elisabeth Paietta, Martin S Tallman, Wendy Stock, Matthew C Foster, Janis Racevskis, Jacob M Rowe, Selina Luger, Steven M Kornblau, Sheila A Shurtleff, Susana C Raimondi, Elaine R Mardis, Richard K Wilson, John E Dick, Stephen P Hunger, Mignon L Loh, James R Downing, Charles G Mullighan
Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL). Here we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion...
October 24, 2016: Nature Genetics
E Pomari, G Basso, S Bresolin, M Pillon, E Carraro, E S d'Amore, G Viola, C Frasson, K Basso, P Bonvini, L Mussolin
Leukemia accepted article preview online, 24 October 2016. doi:10.1038/leu.2016.292.
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Xueyuan Cao, Kristine R Crews, James Downing, Jatinder Lamba, Stanley B Pounds
BACKGROUND: As new technologies allow investigators to collect multiple forms of molecular data (genomic, epigenomic, transcriptomic, etc) and multiple endpoints on a clinical trial cohort, it will become necessary to effectively integrate all these data in a way that reliably identifies biologically important genes. METHODS: We introduce CC-PROMISE as an integrated data analysis method that combines components of canonical correlation (CC) and projection onto the most interesting evidence (PROMISE)...
October 6, 2016: BMC Bioinformatics
Jolanta Skalska-Sadowska, Małgorzata Dawidowska, Bronisława Szarzyńska-Zawadzka, Małgorzata Jarmuż-Szymczak, Joanna Czerwińska-Rybak, Ludomiła Machowska, Katarzyna Derwich
We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1(wt) , FBXW7(wt) , STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations...
October 19, 2016: Pediatric Blood & Cancer
Jesus Duque-Afonso, Chiou-Hong Lin, Kyuho Han, Michael C Wei, Jue Feng, Jason Kurzer, Corina Schneidawind, Stephen H K Wong, Michael C Bassik, Michael L Cleary
There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the fusion protein E2A-PBX1, which is present in 5-7% of pediatric and 50% of pre-B-cell receptor (preBCR+) acute lymphocytic leukemia (ALL). In this study, we describe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL which result in hyperactivation of the key oncogenic effector enzyme PLCγ2...
October 7, 2016: Cancer Research
Jinghua Wu, Shan Jia, Changxi Wang, Wei Zhang, Sixi Liu, Xiaojing Zeng, Huirong Mai, Xiuli Yuan, Yuanping Du, Xiaodong Wang, Xueyu Hong, Xuemei Li, Feiqiu Wen, Xun Xu, Jianhua Pan, Changgang Li, Xiao Liu
Acute B lymphoblastic leukemia (B-ALL) is one of the most common types of childhood cancer worldwide and chemotherapy is the main treatment approach. Despite good response rates to chemotherapy regiments, many patients eventually relapse and minimal residual disease (MRD) is the leading risk factor for relapse. The evolution of leukemic clones during disease development and treatment may have clinical significance. In this study, we performed immunoglobulin heavy chain (IGH) repertoire high throughput sequencing (HTS) on the diagnostic and post-treatment samples of 51 pediatric B-ALL patients...
2016: Frontiers in Immunology
Marcin Braun, Agata Pastorczak, Wojciech Fendler, Joanna Madzio, Bartlomiej Tomasik, Joanna Taha, Marta Bielska, Lukasz Sedek, Tomasz Szczepanski, Michal Matysiak, Katarzyna Derwich, Monika Lejman, Jerzy Kowalczyk, Bernarda Kazanowska, Wanda Badowska, Jan Styczynski, Nina Irga-Jaworska, Joanna Trelinska, Beata Zalewska-Szewczyk, Filip Pierlejewski, Iwona Wlodarska, Wojciech Młynarski
The inactivation of tumor suppressor genes located within 9p21 locus (CDKN2A, CDKN2B) occurs in up to 30% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its independent prognostic significance remains controversial. In order to investigate the prognostic impact of deletions and promoter methylation within 9p21, 641 children with newly diagnosed BCP-ALL using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) were investigated. A total of 169 (26.4%) microdeletions in 9p21 were detected, of which 71 were homozygous...
October 18, 2016: Leukemia & Lymphoma
Michael R Loken, Andrew P Voigt, Lisa Eidenschink Brodersen, Wayne Fritschle, Andrew J Menssen, Denise A Wells
The quantitative expression of cell surface antigens and light scattering properties of five cellular reference populations in stressed bone marrow specimens were compared between pediatric and adult patients treated for acute myeloid leukemia (AML). The mean intensity of each antigen as well as the within patient and between patient variability showed striking consistency between the two different age groups. The only difference between the groups of specimens was the proportion of progenitor cells in the adult cohort averaged less than three times the proportion in the pediatric cohort...
October 18, 2016: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Michael R Loken, Andrew P Voigt, Lisa Eidenschink Brodersen, Wayne Fritschle, Andrew J Menssen, Soheil Meshinchi, Denise A Wells
Five reference populations in bone marrow specimens were identified by flow cytometry using specific combinations of reagents in order define the variation of gene product expression intensities both within and between individuals. Mature lymphocytes, uncommitted progenitor cells, promyelocytes, mature monocytes and mature neutrophils can be reproducibly identified as distinct clusters of events in heterogeneous, maturing bone marrow specimens. Support Vector Machines were used to identify the reference populations in order to reduce subjective bias in manually defining boundaries of these populations since they were not discretely separated from the remainder of the cells...
October 18, 2016: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Anita F Oliveira, Aline Tansini, Daniel O Vidal, Luiz F Lopes, Konradin Metze, Irene Lorand-Metze
BACKGROUND: Immunophenotyping of bone marrow (BM) hemopoietic precursors is useful for diagnosis of adult myelodysplastic syndrome (MDS), but data concerning pediatric patients are limited. We analyzed immunophenotypic features of BM cells at diagnosis of children who were referred to the Brazilian Pediatric Cooperative Group of Myelodysplastic Syndromes. METHODS: Diagnosis was based on clinical information, peripheral blood counts, BM cytology and cytogenetics...
October 17, 2016: Pediatric Blood & Cancer
Xiaoli Wu, Xuefeng Feng, Xiaoqing Zhao, Futian Ma, Na Liu, Hongming Guo, Chaonan Li, Huan Du, Baoxi Zhang
BACKGROUND/AIMS: Acute and chronic leukemia are severe malignant cancers worldwide, and can occur in pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia (PL) remains challenging. Autophagy is essential for the regulation of cell survival in the harsh environment. However, the role of autophagy in the survival of PL cells under the oxidative stress, e.g. chemotherapy, remain ill-defined...
October 17, 2016: Cellular Physiology and Biochemistry
N Narayan, L Morenos, B Phipson, S N Willis, G Brumatti, S Eggers, N Lalaoui, L M Brown, H J Kosasih, R C Bartolo, L Zhou, D Catchpoole, R Saffery, A Oshlack, G J Goodall, P G Ekert
Enforced expression of miR-155 in myeloid cells has been shown to have both oncogenic or tumour suppressor functions in acute myeloid leukemia (AML). We sought to resolve these contrasting effects of miR-155 overexpression using murine models of AML and human paediatric AML datasets. We show that the highest miR-155 expression levels inhibited proliferation in murine AML models. Over time, enforced miR-155 expression in AML in vitro and in vivo, however, favors selection of intermediate miR-155 expression levels that results in increased tumour burden in mice, without accelerating the onset of disease...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Xiang Wang, Dongjian Zuo, Yufang Yuan, Xiaochun Yang, Ze Hong, Rongrong Zhang
PURPOSE: The aim of this study was to investigate roles of microRNA (miR)-183 in pediatric acute myeloid leukemia (AML). METHODS: miR-183 expression in bone marrow and patients' sera of childhood AML was detected by real-time quantitative PCR. Functions of miR-183 in malignant phenotypes of two leukemia cell lines were then evaluated. Additionally, putative targets of miR-183 were predicted using three miRNA target prediction algorithms and validated by luciferase reporter assay...
October 13, 2016: Journal of Cancer Research and Clinical Oncology
M-W Jin, S-M Xu, Q An, P Wang
OBJECTIVE: Leukemia is the most common cancer of childhood, with AML, CML, ALL and CLL being the most common. Environmental and genetic factors have been studied extensively in children with childhood leukemia. Other factors, such as the prenatal parental use of controlled substances, have not been investigated to the same degree. We review what is currently known about environmental and parental factors and the occurrence of leukemia in children. MATERIALS AND METHODS: Electronic databases were searched for studies correlated pediatric leukemia with (1) ionizing radiation; (2) benzene; (3) parental drug use (4) parental alcohol use; (5) genetic factors...
September 2016: European Review for Medical and Pharmacological Sciences
E Waanders, B Scheijen, M C J Jongmans, H Venselaar, S V van Reijmersdal, A H A van Dijk, A Pastorczak, R D A Weren, C E van der Schoot, M van de Vorst, E Sonneveld, N Hoogerbrugge, V H J van der Velden, B Gruhn, P M Hoogerbrugge, J J M van Dongen, A G van Kessel, F N van Leeuwen, R P Kuiper
The contribution of genetic predisposing factors to the development of pediatric acute lymphoblastic leukemia (ALL), the most frequently diagnosed cancer in childhood, has not been fully elucidated. Children presenting with multiple de novo leukemias are more likely to suffer from genetic predisposition. Here, we selected five of these patients and analyzed the mutational spectrum of normal and malignant tissues. In two patients, we identified germline mutations in TYK2, a member of the JAK tyrosine kinase family...
October 13, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Aaron Smith, Vikrum Thimmappa, Brandon Shepherd, Meredith Ray, Anthony Sheyn, Jerome Thompson
BACKGROUND: Invasive fungal sinusitis (IFS) represents an often fatal condition within the pediatric population. In an effort to characterize demographics, treatment modalities, and prognostic factors, we performed a systematic review. METHODS: We systematically reviewed EMBASE, Medline, TRIPdatabase, SCOPUS and the Cochrane database for invasive fungal nasal and sinus infections limited to individuals <18 years of age. Case series including 3 or more patients were included...
November 2016: International Journal of Pediatric Otorhinolaryngology
Brian Y Chan, Kara G Gill, Susan L Rebsamen, Jie C Nguyen
The bone marrow is one of the largest organs in the body and is visible in every magnetic resonance (MR) imaging study. It is composed of a combination of hematopoietic red marrow and fatty yellow marrow, and its composition changes throughout life in response to normal maturation (red to yellow conversion) and stress (yellow to red reconversion). MR imaging is highly sensitive for detection of altered marrow signal intensity, and the T1-weighted spin-echo sequence provides the most robust contrast between yellow marrow and disease...
October 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Chandrika Gowda, Mansi Sachdev, Sunil Muthisami, Malika Kapadia, Lidija Petrovic-Dovat, Melanie Hartman, Yali Ding, Chunhua Song, Jonathon L Payne, Bi-Hua Tan, Sinisa Dovat
BACKGROUND: Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies including breast, prostate, and lung cancer are being tested. Although many CK2 inhibitors exist, only a few have emerged as selective inhibitors that are potent and effective...
October 6, 2016: Current Pharmaceutical Design
Michele N Edison, M Cody O'Dell, Haley P Letter, Kurt Scherer, Jennifer L Williams
An 8-year-old girl presented with bilateral breast masses and was subsequently diagnosed with juvenile myelomonocytic leukemia. Juvenile myelomonocytic leukemia is a rare myelodysplastic syndrome that typically presents in boys younger than 3 years of age with splenomegaly, lymphadenopathy and skin findings. Bilateral breast masses in a child are rare and, as such, present a diagnostic dilemma due to the relative paucity of cases in the literature. We present a case of granulocytic sarcoma of the breasts in a patient with juvenile myelomonocytic leukemia...
October 7, 2016: Pediatric Radiology
Judith Feucht, Simone Kayser, David Gorodezki, Mohamad Hamieh, Michaela Döring, Franziska Blaeschke, Patrick Schlegel, Hans Bösmüller, Leticia Quintanilla-Fend, Martin Ebinger, Peter Lang, Rupert Handgretinger, Tobias Feuchtinger
T-cell immunotherapies are promising options in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We investigated the effect of co-signaling molecules on T-cell attack against leukemia mediated by CD19/CD3-bispecific T-cell engager. Primary CD19+ ALL blasts (n≥10) and physiologic CD19+CD10+ bone marrow precursors were screened for 20 co-signaling molecules. PD-L1, PD-1, LAG-3, CD40, CD86, CD27, CD70 and HVEM revealed different stimulatory and inhibitory profiles of pediatric ALL compared to physiologic cells, with PD-L1 and CD86 as most prominent inhibitory and stimulatory markers...
September 30, 2016: Oncotarget
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