Intragenic PAX5 amplification defines a novel, relapse-prone subtype of B-cell precursor acute lymphoblastic leukemia with a poor outcome.

Centro Ricerca Tettamanti Clinica Pediatrica Università di Milano Bicocca Monza Italy

Childhood Leukaemia Investigation Prague Department of Pediatric Hematology Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Children's Cancer Institute Lowy Cancer Research Centre University of New South Wales Sydney Australia

Children's Cancer Research Institute St Anna Kinderkrebsforschung Vienna Austria

Clinical Genetics Section Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden

Clinical Research Center Nagoya Medical Center National Hospital Organization Aichi Japan

Département de Génétique Hôpital Robert Debré Assistance Publique Hôpitaux de Paris Paris France

Department of Hematology Universitair Ziekenhuis Brussel Vrije Universiteit Brussel Brussels Belgium

Department of Human Genetics Radboud University Medical Center Radboud Institute for Molecular Life Sciences Nijmegen The Netherlands

Department of Pediatric Hematology and Oncology Medical School Hannover Hannover Germany

Department of Pediatric Hematology and Oncology National Center for Child Health and Development Tokyo Japan

Department of Pediatric Hematology and Oncology St Anna Children's Hospital Medical University of Vienna Austria; and

Department of Pediatric Oncology Erasmus MC Sophia Children's Hospital Rotterdam The Netherlands

Department of Pediatrics Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan

Department of Pediatrics Oncology Hematology and Diabetology Medical University of Lodz Lodz Poland

Department of Pediatrics University Hospital Schleswig Holstein Kiel Germany

Division of Oncology and Hematology Department of Pediatrics Charité Universitätsmedizin Berlin Berlin Germany

Dutch Childhood Oncology Group The Hague The Netherlands

German Cancer Consortium and German Cancer Research Center Heidelberg Germany

INSERM Unité Mixte de Recherché 1131 Institut Universitaire d'Hématologie Université Paris Diderot Paris Sorbonne Cité Paris France

Leukaemia Research Cytogenetics Group Wolfson Childhood Cancer Research Centre Northern Institute for Cancer Research Newcastle University Newcastle upon Tyne United Kingdom

Pediatric Hematology Oncology Program Research Center Instituto Nacional de Câncer Rio de Janeiro Brazil

Pediatric Oncology Children's Research Centre University Children's Hospital Zürich Zürich Switzerland

Zobrazit více v PubMed

Moorman AV. The clinical relevance of chromosomal and genomic abnormalities in B-cell precursor acute lymphoblastic leukaemia. Blood Rev. 2012;26(3):123-135. PubMed

Medvedovic J, Ebert A, Tagoh H, Busslinger M. Pax5: a master regulator of B cell development and leukemogenesis. Adv Immunol. 2011;111:179-206. PubMed

Schwab CJ, Chilton L, Morrison H, et al. . Genes commonly deleted in childhood B-cell precursor acute lymphoblastic leukemia: association with cytogenetics and clinical features. Haematologica. 2013;98(7):1081-1088. PubMed PMC

Mullighan CG, Goorha S, Radtke I, et al. . Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature. 2007;446(7137):758-764. PubMed

Den Boer ML, van Slegtenhorst M, De Menezes RX, et al. . A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol. 2009;10(2):125-134. PubMed PMC

Shah S, Schrader KA, Waanders E, et al. . A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nat Genet. 2013;45(10):1226-1231. PubMed PMC

Auer F, Rüschendorf F, Gombert M, et al. . Inherited susceptibility to pre B-ALL caused by germline transmission of PAX5 c.547G>A. Leukemia. 2014;28(5):1136-1138. PubMed

Coyaud E, Struski S, Prade N, et al. . Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study. Blood. 2010;115(15):3089-3097. PubMed

Nebral K, Denk D, Attarbaschi A, et al. . Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia. Leukemia. 2009;23(1):134-143. PubMed

Kurahashi S, Hayakawa F, Miyata Y, et al. . PAX5-PML acts as a dual dominant-negative form of both PAX5 and PML. Oncogene. 2011;30(15):1822-1830. PubMed

Fortschegger K, Anderl S, Denk D, Strehl S. Functional heterogeneity of PAX5 chimeras reveals insight for leukemia development. Mol Cancer Res. 2014;12(4):595-606. PubMed

Fazio G, Cazzaniga V, Palmi C, et al. . PAX5/ETV6 alters the gene expression profile of precursor B cells with opposite dominant effect on endogenous PAX5. Leukemia. 2013;27(4):992-995. PubMed

Krentz S, Hof J, Mendioroz A, et al. . Prognostic value of genetic alterations in children with first bone marrow relapse of childhood B-cell precursor acute lymphoblastic leukemia. Leukemia. 2013;27(2):295-304. PubMed

van der Veer A, Waanders E, Pieters R, et al. . Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL. Blood. 2013;122(15):2622-2629. PubMed PMC

Schwab CJ, Jones LR, Morrison H, et al. . Evaluation of multiplex ligation-dependent probe amplification as a method for the detection of copy number abnormalities in B-cell precursor acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2010;49(12):1104-1113. PubMed

Familiades J, Bousquet M, Lafage-Pochitaloff M, et al. . PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1 fusion genes: a GRAALL study. Leukemia. 2009;23(11):1989-1998. PubMed

Ofverholm I, Tran AN, Heyman M, et al. . Impact of IKZF1 deletions and PAX5 amplifications in pediatric B-cell precursor ALL treated according to NOPHO protocols. Leukemia. 2013;27(9):1936-1939. PubMed

Sulong S, Moorman AV, Irving JA, et al. . A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups. Blood. 2009;113(1):100-107. PubMed

Harris RL, Harrison CJ, Martineau M, Taylor KE, Moorman AV. Is trisomy 5 a distinct cytogenetic subgroup in acute lymphoblastic leukemia? Cancer Genet Cytogenet. 2004;148(2):159-162. PubMed

Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013;14(6):e205-e217. PubMed

Moorman AV, Enshaei A, Schwab C, et al. . A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia. Blood. 2014;124(9):1434-1444. PubMed

Mullighan CG, Su X, Zhang J, et al. ; Children’s Oncology Group. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470-480. PubMed PMC

Dun KA, Vanhaeften R, Batt TJ, Riley LA, Diano G, Williamson J. BCR-ABL1 gene rearrangement as a subclonal change in ETV6-RUNX1–positive B-cell acute lymphoblastic leukemia. Blood Adv. 2016;1(2):132-138. PubMed PMC

Morak M, Attarbaschi A, Fischer S, et al. . Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2-harboring clones as main relapse-driving force in childhood ALL. Blood. 2012;120(26):5134-5142. PubMed PMC

PAX5::AUTS2 childhood B-ALL: a relapse-prone genetic subtype with frequent central nervous system involvement and a poor outcome

Genomic landscape of pediatric B-other acute lymphoblastic leukemia in a consecutive European cohort

Validation of the United Kingdom copy-number alteration classifier in 3239 children with B-cell precursor ALL

New biological and genetic classification and therapeutically relevant categories in childhood B-cell precursor acute lymphoblastic leukemia