Grant Number:	1R01CA089032-01 Interpret this number
Primary Investigator:	Wiemels, Joseph
Organization:	Univ Of California At San Francisco
Project Title:	Backtracking Translocations in Childhood Leukemia
Fiscal Year:	2001

DESCRIPTION (Adapted from investigator's abstract): The etiology of childhood leukemia is currently being examined under large-scale epidemiology studies in the US and UK. The investigator proposes to examine the timing and etiology of the most frequent genetic aberrations in childhood acute lymphoblastic and myeloblastic leukemia (ALL and AML) by using molecular biology and bioinformatic tools and resources in patient diagnostic and archived materials. The investigator has previously shown that the most common translocation in childhood leukemia, t(12;21) (or TEL-AML1 gene fusion) can occur before birth in a small number of individuals who later developed childhood leukemia. These studies will be expanded and extended to an independent population in California. About 150 patients with specific aberrations, including t(12;21), t(1;19), t(8;21), and NRAS mutations, will be "backtracked" by screening for the aberration in the neonatal heel-prick Guthrie spots that were taken at birth. The aberrations will first be characterized at the genomic DNA level, and then will be used as clonotypic markers in sensitive screening assays of Guthrie spots. In addition to this use as markers of leukemia cell clones, translocation fusion sequences provide insight into the processes that formed the fusion. TEL-AML1 fusion junctions tend to group into "micro-clusters," or distinct regions within the larger intronic breakpoint cluster regions. The micro-clustering is independent of the structure of the chimeric oncogenic protein, which is the same for all patients. Micro-clustering of breakpoints in certain areas suggests that features of the intrinsic DNA sequence or chromatin structure are critical in the process of formation of the translocation. These features will be probed by statistically based DNA sequence recognition tools along with a coordinated laboratory analysis to identify sequence motifs. A final goal of the project is to develop methods to sensitively track leukemia clones in treated patients in order to gauge the success of therapy. In summary, this project aims to elucidate the timing and structure of the genetic events that lead to childhood leukemia.




Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein.
Authors: Diakos C. , Xiao Y. , Zheng S. , Kager L. , Dworzak M. , Wiemels J.L. .
Source: Plos One, 2014; 9(2), p. e87602.
EPub date: 2014-02-04 00:00:00.0.
PMID: 24503810
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Unusual Space-time Patterning Of The Fallon, Nevada Leukemia Cluster: Evidence Of An Infectious Etiology
Authors: Francis S.S. , Selvin S. , Yang W. , Buffler P.A. , Wiemels J.L. .
Source: Chemico-biological Interactions, 2012-04-05 00:00:00.0; 196(3), p. 102-9.
PMID: 21352818
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TEL-AML1 regulation of survivin and apoptosis via miRNA-494 and miRNA-320a.
Authors: Diakos C. , Zhong S. , Xiao Y. , Zhou M. , Vasconcelos G.M. , Krapf G. , Yeh R.F. , Zheng S. , Kang M. , Wiencke J.K. , et al. .
Source: Blood, 2010-12-02 00:00:00.0; 116(23), p. 4885-93.
EPub date: 2010-12-02 00:00:00.0.
PMID: 20807887
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Backtracking Ras Mutations In High Hyperdiploid Childhood Acute Lymphoblastic Leukemia
Authors: Wiemels J.L. , Kang M. , Chang J.S. , Zheng L. , Kouyoumji C. , Zhang L. , Smith M.T. , Scelo G. , Metayer C. , Buffler P. , et al. .
Source: Blood Cells, Molecules & Diseases, 2010-10-15 00:00:00.0; 45(3), p. 186-91.
PMID: 20688547
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Analysis Of Genomic Breakpoints In P190 And P210 Bcr-abl Indicate Distinct Mechanisms Of Formation
Authors: Score J. , Calasanz M.J. , Ottman O. , Pane F. , Yeh R.F. , Sobrinho-Simões M.A. , Kreil S. , Ward D. , Hidalgo-Curtis C. , Melo J.V. , et al. .
Source: Leukemia, 2010 Oct; 24(10), p. 1742-50.
PMID: 20703256
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Flt3 Mutation Incidence And Timing Of Origin In A Population Case Series Of Pediatric Leukemia
Authors: Chang P. , Kang M. , Xiao A. , Chang J. , Feusner J. , Buffler P. , Wiemels J. .
Source: Bmc Cancer, 2010; 10, p. 513.
PMID: 20875128
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IgE, allergy, and risk of glioma: update from the San Francisco Bay Area Adult Glioma Study in the temozolomide era.
Authors: Wiemels J.L. , Wilson D. , Patil C. , Patoka J. , McCoy L. , Rice T. , Schwartzbaum J. , Heimberger A. , Sampson J.H. , Chang S. , et al. .
Source: International Journal Of Cancer, 2009-08-01 00:00:00.0; 125(3), p. 680-7.
PMID: 19408307
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Allergies And Childhood Leukemia
Authors: Chang J.S. , Wiemels J.L. , Buffler P.A. .
Source: Blood Cells, Molecules & Diseases, 2009 Mar-Apr; 42(2), p. 99-104.
PMID: 19049852
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Reproductive factors and hormone use and risk of adult gliomas.
Authors: Felini M.J. , Olshan A.F. , Schroeder J.C. , Carozza S.E. , Miike R. , Rice T. , Wrensch M. .
Source: Cancer Causes & Control : Ccc, 2009 Feb; 20(1), p. 87-96.
PMID: 18766447
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The molecular anatomy of the FIP1L1-PDGFRA fusion gene.
Authors: Walz C. , Score J. , Mix J. , Cilloni D. , Roche-Lestienne C. , Yeh R.F. , Wiemels J.L. , Ottaviani E. , Erben P. , Hochhaus A. , et al. .
Source: Leukemia, 2009 Feb; 23(2), p. 271-8.
PMID: 18987651
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Backtracking Of Leukemic Clones To Birth
Authors: Wiemels J. , Kang M. , Greaves M. .
Source: Methods In Molecular Biology (clifton, N.j.), 2009; 538, p. 7-27.
PMID: 19277581
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NQO1 polymorphisms and de novo childhood leukemia: a HuGE review and meta-analysis.
Authors: Guha N. , Chang J.S. , Chokkalingam A.P. , Wiemels J.L. , Smith M.T. , Buffler P.A. .
Source: American Journal Of Epidemiology, 2008-12-01 00:00:00.0; 168(11), p. 1221-32.
EPub date: 2008-12-01 00:00:00.0.
PMID: 18945694
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Chromosome 12p deletions in TEL-AML1 childhood acute lymphoblastic leukemia are associated with retrotransposon elements and occur postnatally.
Authors: Wiemels J.L. , Hofmann J. , Kang M. , Selzer R. , Green R. , Zhou M. , Zhong S. , Zhang L. , Smith M.T. , Marsit C. , et al. .
Source: Cancer Research, 2008-12-01 00:00:00.0; 68(23), p. 9935-44.
PMID: 19047175
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Adenovirus detection in Guthrie cards from paediatric leukaemia cases and controls.
Authors: Vasconcelos G.M. , Kang M. , Pombo-de-Oliveira M.S. , Schiffman J.D. , Lorey F. , Buffler P. , Wiemels J.L. .
Source: British Journal Of Cancer, 2008-11-18 00:00:00.0; 99(10), p. 1668-72.
EPub date: 2008-11-18 00:00:00.0.
PMID: 19002185
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Pathway analysis of single-nucleotide polymorphisms potentially associated with glioblastoma multiforme susceptibility using random forests.
Authors: Chang J.S. , Yeh R.F. , Wiencke J.K. , Wiemels J.L. , Smirnov I. , Pico A.R. , Tihan T. , Patoka J. , Miike R. , Sison J.D. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2008 Jun; 17(6), p. 1368-73.
PMID: 18559551
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Line Region Hypomethylation Is Associated With Lifestyle And Differs By Human Papillomavirus Status In Head And Neck Squamous Cell Carcinomas
Authors: Furniss C.S. , Marsit C.J. , Houseman E.A. , Eddy K. , Kelsey K.T. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2008 Apr; 17(4), p. 966-71.
PMID: 18398038
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Allergy-related polymorphisms influence glioma status and serum IgE levels.
Authors: Wiemels J.L. , Wiencke J.K. , Kelsey K.T. , Moghadassi M. , Rice T. , Urayama K.Y. , Miike R. , Wrensch M. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2007 Jun; 16(6), p. 1229-35.
PMID: 17548690
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Nonsynonymous coding single-nucleotide polymorphisms spanning the genome in relation to glioblastoma survival and age at diagnosis.
Authors: Wrensch M. , McMillan A. , Wiencke J. , Wiemels J. , Kelsey K. , Patoka J. , Jones H. , Carlton V. , Miike R. , Sison J. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2007-01-01 00:00:00.0; 13(1), p. 197-205.
PMID: 17200355
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Accuracy Of Multiplexed Illumina Platform-based Single-nucleotide Polymorphism Genotyping Compared Between Genomic And Whole Genome Amplified Dna Collected From Multiple Sources
Authors: Paynter R.A. , Skibola D.R. , Skibola C.F. , Buffler P.A. , Wiemels J.L. , Smith M.T. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2006 Dec; 15(12), p. 2533-6.
PMID: 17164381
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Serum IgE, tumor epidermal growth factor receptor expression, and inherited polymorphisms associated with glioma survival.
Authors: Wrensch M. , Wiencke J.K. , Wiemels J. , Miike R. , Patoka J. , Moghadassi M. , McMillan A. , Kelsey K.T. , Aldape K. , Lamborn K.R. , et al. .
Source: Cancer Research, 2006-04-15 00:00:00.0; 66(8), p. 4531-41.
PMID: 16618782
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Diagnostic, treatment, and demographic factors influencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area.
Authors: Wrensch M. , Rice T. , Miike R. , McMillan A. , Lamborn K.R. , Aldape K. , Prados M.D. .
Source: Neuro-oncology, 2006 Jan; 8(1), p. 12-26.
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DNA topoisomerase II in therapy-related acute promyelocytic leukemia.
Authors: Mistry A.R. , Felix C.A. , Whitmarsh R.J. , Mason A. , Reiter A. , Cassinat B. , Parry A. , Walz C. , Wiemels J.L. , Segal M.R. , et al. .
Source: The New England Journal Of Medicine, 2005-04-14 00:00:00.0; 352(15), p. 1529-38.
PMID: 15829534
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RAS mutation is associated with hyperdiploidy and parental characteristics in pediatric acute lymphoblastic leukemia.
Authors: Wiemels J.L. , Zhang Y. , Chang J. , Zheng S. , Metayer C. , Zhang L. , Smith M.T. , Ma X. , Selvin S. , Buffler P.A. , et al. .
Source: Leukemia, 2005 Mar; 19(3), p. 415-9.
PMID: 15674422
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Reduced immunoglobulin E and allergy among adults with glioma compared with controls.
Authors: Wiemels J.L. , Wiencke J.K. , Patoka J. , Moghadassi M. , Chew T. , McMillan A. , Miike R. , Barger G. , Wrensch M. .
Source: Cancer Research, 2004-11-15 00:00:00.0; 64(22), p. 8468-73.
PMID: 15548720
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Prenatal origin of childhood acute myeloid leukemias harboring chromosomal rearrangements t(15;17) and inv(16).
Authors: McHale C.M. , Wiemels J.L. , Zhang L. , Ma X. , Buffler P.A. , Feusner J. , Matthay K. , Dahl G. , Smith M.T. .
Source: Blood, 2003-06-01 00:00:00.0; 101(11), p. 4640-1.
PMID: 12756163
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Prenatal Origin Of Tel-aml1-positive Acute Lymphoblastic Leukemia In Children Born In California
Authors: McHale C.M. , Wiemels J.L. , Zhang L. , Ma X. , Buffler P.A. , Guo W. , Loh M.L. , Smith M.T. .
Source: Genes, Chromosomes & Cancer, 2003 May; 37(1), p. 36-43.
PMID: 12661004
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Genomic anatomy of the specific reciprocal translocation t(15;17) in acute promyelocytic leukemia.
Authors: Reiter A. , Saussele S. , Grimwade D. , Wiemels J.L. , Segal M.R. , Lafage-Pochitaloff M. , Walz C. , Weisser A. , Hochhaus A. , Willer A. , et al. .
Source: Genes, Chromosomes & Cancer, 2003 Feb; 36(2), p. 175-88.
PMID: 12508246
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TEL-AML1 fusion precedes differentiation to pre-B cells in childhood acute lymphoblastic leukemia.
Authors: Pine S.R. , Wiemels J.L. , Jayabose S. , Sandoval C. .
Source: Leukemia Research, 2003 Feb; 27(2), p. 155-64.
PMID: 12526921
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Real-time quantitative PCR: standardized detection of minimal residual disease in pediatric acute lymphoblastic leukemia. Polymerase chain reaction.
Authors: Pine S.R. , Moy F.H. , Wiemels J.L. , Gill R.K. , Levendoglu-Tugal O. , Ozkaynak M.F. , Sandoval C. , Jayabose S. .
Source: Journal Of Pediatric Hematology/oncology, 2003 Feb; 25(2), p. 103-8.
PMID: 12571459
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Site-specific Translocation And Evidence Of Postnatal Origin Of The T(1;19) E2a-pbx1 Fusion In Childhood Acute Lymphoblastic Leukemia
Authors: Wiemels J.L. , Leonard B.C. , Wang Y. , Segal M.R. , Hunger S.P. , Smith M.T. , Crouse V. , Ma X. , Buffler P.A. , Pine S.R. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2002-11-12 00:00:00.0; 99(23), p. 15101-6.
PMID: 12415113
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In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia.
Authors: Wiemels J.L. , Xiao Z. , Buffler P.A. , Maia A.T. , Ma X. , Dicks B.M. , Smith M.T. , Zhang L. , Feusner J. , Wiencke J. , et al. .
Source: Blood, 2002-05-15 00:00:00.0; 99(10), p. 3801-5.
PMID: 11986239
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History of allergies among adults with glioma and controls.
Authors: Wiemels J.L. , Wiencke J.K. , Sison J.D. , Miike R. , McMillan A. , Wrensch M. .
Source: International Journal Of Cancer, 2002-04-01 00:00:00.0; 98(4), p. 609-15.
PMID: 11920623
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Molecular characterization of genomic AML1-ETO fusions in childhood leukemia.
Authors: Xiao Z. , Greaves M.F. , Buffler P. , Smith M.T. , Segal M.R. , Dicks B.M. , Wiencke J.K. , Wiemels J.L. .
Source: Leukemia, 2001 Dec; 15(12), p. 1906-13.
PMID: 11753612
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