Mutations of the TP53 gene in acute myeloid leukemia are strongly associated with a complex aberrant karyotype.
TLDR
It is demonstrated that TP53 mutations are very rare in AML without a complex aberrant karyotype (4/193, 2.1%) and coincidence with other molecular mutations were rare.Abstract:
In acute myeloid leukemia (AML) with complex aberrant karyotype, a loss of one TP53 allele is frequently observed. We analyzed the incidence of TP53 mutations and deletions in 107 AML with complex aberrant karyotype. In 50 of 57 cases showing a loss of one TP53 allele, a TP53 mutation was detected in the remaining allele. In addition, in 33 of 50 cases with two TP53 copies, a TP53 mutation was found. Therefore, the frequency of TP53 mutations in AML with complex aberrant karyotype was 78%. In a second step, we analyzed TP53 mutations in a cohort of AML comprising different cytogenetic subgroups. TP53 mutations were detected in 33 of 235 cases (14%). Coincidences with other molecular mutations were rare. We confirmed a high incidence of TP53 mutations in AML with a complex aberrant karyotype (29/42, 69%) and demonstrated that TP53 mutations are very rare in AML without a complex aberrant karyotype (4/193, 2.1%).read more
Citations
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Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
Hartmut Döhner,Elihu H. Estey,David Grimwade,Sergio Amadori,Frederick R. Appelbaum,Thomas Büchner,Hervé Dombret,Benjamin L. Ebert,Pierre Fenaux,Richard A. Larson,Ross L. Levine,Francesco Lo-Coco,Tomoki Naoe,Dietger Niederwieser,Gert J. Ossenkoppele,Miguel A. Sanz,Jorge Sierra,Martin S. Tallman,Hwei-Fang Tien,Andrew H. Wei,Andrew H. Wei,Bob Löwenberg,Clara D. Bloomfield +22 more
TL;DR: An international panel to provide updated evidence- and expert opinion-based recommendations for diagnosis and management of acute myeloid leukemia in adults includes a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease.
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Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations
Tobias Rausch,David T.W. Jones,Marc Zapatka,Adrian M. Stütz,Thomas Zichner,Joachim Weischenfeldt,Natalie Jäger,Marc Remke,David Shih,Paul A. Northcott,Elke Pfaff,Jelena Tica,Qi Wang,Luca Massimi,Hendrik Witt,Sebastian Bender,Sabrina Pleier,Huriye Cin,Cynthia Hawkins,Christian Beck,Andreas von Deimling,Volkmar Hans,Benedikt Brors,Roland Eils,Wolfram Scheurlen,Jonathon Blake,Vladimir Benes,Andreas E. Kulozik,Olaf Witt,Olaf Witt,Dianna Martin,Cindy Zhang,Rinnat Porat,Diana M. Merino,Jonathan D. Wasserman,Nada Jabado,Adam M. Fontebasso,Lars Bullinger,Frank G. Rücker,Konstanze Döhner,Hartmut Döhner,Jan Koster,Jan J. Molenaar,Rogier Versteeg,Marcel Kool,Uri Tabori,David Malkin,Andrey Korshunov,Michael D. Taylor,Peter Lichter,Stefan M. Pfister,Jan O. Korbel +51 more
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TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome.
Frank G. Rücker,Richard F. Schlenk,Lars Bullinger,Sabine Kayser,Veronica Teleanu,Helena Kett,Marianne Habdank,Carla Maria Kugler,Karlheinz Holzmann,Verena I. Gaidzik,Peter Paschka,Gerhard Held,Marie von Lilienfeld-Toal,Michael Lübbert,Stefan Fröhling,Thorsten Zenz,Thorsten Zenz,Jürgen Krauter,Brigitte Schlegelberger,Arnold Ganser,Peter Lichter,Konstanze Döhner,Hartmut Döhner +22 more
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Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications.
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New mutations and pathogenesis of myeloproliferative neoplasms.
William Vainchenker,William Vainchenker,François Delhommeau,François Delhommeau,Stefan N. Constantinescu,Stefan N. Constantinescu,Olivier Bernard,Olivier Bernard,Olivier Bernard +8 more
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References
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Surfing the p53 network
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Journal ArticleDOI
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Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461)
John C. Byrd,Krzysztof Mrózek,Richard K. Dodge,Andrew J. Carroll,Colin G. Edwards,Diane C. Arthur,Mark J. Pettenati,Shivanand R. Patil,Kathleen W. Rao,Michael S. Watson,Prasad Koduru,Joseph O. Moore,Richard Stone,Robert J. Mayer,Eric J. Feldman,Frederick R. Davey,Charles A. Schiffer,Richard A. Larson,Clara D. Bloomfield +18 more
TL;DR: In this paper, the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, 5-year cumulative incidence of relapse (CIR), and 5-to-5-year overall survival (OS) of acute myeloid leukemia (AML) patients was investigated.
Journal ArticleDOI
Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study
Marilyn L. Slovak,Kenneth J. Kopecky,Peter A. Cassileth,David H. Harrington,Karl S. Theil,Anwar Mohamed,Elizabeth Paietta,Cheryl L. Willman,David R. Head,Jacob M. Rowe,Stephen J. Forman,Frederick R. Appelbaum +11 more
TL;DR: Cytogenetic risk status is a significant factor in predicting response of AML patients to therapy; however, to tighten treatment correlates within genetically defined AML subsets, a significantly larger leukemia cytogenetic database is warranted.
Journal ArticleDOI
The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial.
David Grimwade,Helen Walker,G Harrison,Fiona Oliver,S Chatters,Christine J. Harrison,Keith Wheatley,Alan Kenneth Burnett,Anthony H. Goldstone +8 more
TL;DR: This study suggests that hierarchical cytogenetic classification identifies biologically distinct subsets of AML that are represented in all age groups, and highlights the importance of karyotype as a critical independent determinant of outcome in older patients with AML.
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