Clonal dynamics in pediatric B-cell precursor acute lymphoblastic leukemia with very early relapse.
RAD21
TP53
WHSC1
clonal dynamics
pediatric acute lymphoblastic leukemia
very early relapse
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
18
08
2021
received:
08
05
2021
accepted:
31
08
2021
pubmed:
2
10
2021
medline:
4
3
2022
entrez:
1
10
2021
Statut:
ppublish
Résumé
One-quarter of the relapses in children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) occur very early (within 18 months, before completion of treatment), and prognosis in these patients is worse compared to cases that relapse after treatment has ended. In this study, we performed a genomic analysis of diagnosis-relapse pairs of 12 children who relapsed very early, followed by a deep-sequencing validation of all identified mutations. In addition, we included one case with a good initial treatment response and on-treatment relapse at the end of upfront therapy. We observed a dynamic clonal evolution in all cases, with relapse almost exclusively originating from a subclone at diagnosis. We identified several driver mutations that may have influenced the outgrowth of a minor clone at diagnosis to become the major clone at relapse. For example, a minimal residual disease (MRD)-based standard-risk patient with ETV6-RUNX1-positive leukemia developed a relapse from a TP53-mutated subclone after loss of the wildtype allele. Furthermore, two patients with TCF3-PBX1-positive leukemia that developed a very early relapse carried E1099K WHSC1 mutations at diagnosis, a hotspot mutation that was recurrently encountered in other very early TCF3-PBX1-positive leukemia relapses as well. In addition to alterations in known relapse drivers, we found two cases with truncating mutations in the cohesin gene RAD21. Comprehensive genomic characterization of diagnosis-relapse pairs shows that very early relapses in BCP-ALL frequently arise from minor subclones at diagnosis. A detailed understanding of the therapeutic pressure driving these events may aid the development of improved therapies.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29361Informations de copyright
© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.
Références
Barr RD, Ferrari A, Ries L, Whelan J, Bleyer WA Cancer in adolescents and young adults: a narrative review of the current status and a view of the future. JAMA Pediatr. 2016;170:495-501.
Katanoda K, Shibata A, Matsuda T, et al. Childhood, adolescent and young adult cancer incidence in Japan in 2009-2011. Jpn J Clin Oncol. 2017;47:762-771.
Ward E, DeSantis C, Robbins A, Kohler B, Jemal A. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin. 2014:64;83-103.
Steliarova-Foucher E, Colombet M, Ries LAG, et al. International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol. 2017:18:719-731.
Pieters R, de Groot-Kruseman H, Van der Velden V, et al. Successful therapy reduction and intensification for childhood acute lymphoblastic leukemia based on minimal residual disease monitoring: study ALL10 from the Dutch Childhood Oncology Group. J Clin Oncol. 2016:34:2591-2601.
Hunger SP, Lu X, Devidas M, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012;30:1663-1669.
Ma X, Edmonson M, Yergeau D, et al. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia. Nat Commun. 2015;6:6604.
Waanders E, Gu Z, Dobson SM, et al. Mutational landscape and patterns of clonal evolution in relapsed pediatric acute lymphoblastic leukemia. Blood Cancer Discov. 2020;1:96-111.
Mullighan CG, Zhang J, Kasper LH, et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature. 2011;471:235-239.
Tzoneva G, Perez-Garcia A, Carpenter Z, et al. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nat Med. 2013;19:368-371.
Kuiper RP, Waanders E, van der Velden VH, et al. IKZF1 deletions predict relapse in uniformly treated pediatric precursor B-ALL. Leukemia. 2010;24:1258-1264.
Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360:470-480.
Tzoneva G, Dieck CL, Oshima K, et al. Clonal evolution mechanisms in NT5C2 mutant-relapsed acute lymphoblastic leukaemia. Nature. 2018;553:511-514.
Meyer JA, Wang J, Hogan LE, et al. Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat Genet. 2013;45:290-294.
Polak R, de Rooij B, Pieters R, den Boer ML. B-cell precursor acute lymphoblastic leukemia cells use tunneling nanotubes to orchestrate their microenvironment. Blood. 2015;126:2404-2414.
Iwamoto S, Mihara K, Downing JR, Pui C-H, Campana D. Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase. J Clin Invest. 2007;117:1049-1057.
Cahu X, Calvo J, Poglio S, et al. Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia. Blood Adv. 2017;1:1760-1772.
Tallen G, Ratei R, Mann G, et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010;28:2339-2347.
Oskarsson T, Söderhäll S, Arvidson J, et al. Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2018;65:e26909.
Oskarsson T, Söderhäll S, Arvidson J, et al. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome. Haematologica. 2016;101:68-76.
Benard-Slagter A, Zondervan I, de Groot K, et al. Digital multiplex ligation-dependent probe amplification for detection of key copy number alterations in T- and B-cell lymphoblastic leukemia. J Mol Diagn. 2017;19:659-672.
Miller CA, McMichael J, Dang HX, et al. Visualizing tumor evolution with the fishplot package for R. BMC Genomics. 2016;17:880.
Blokzijl F, Janssen R, van Boxtel R, Cuppen E MutationalPatterns: comprehensive genome-wide analysis of mutational processes. Genome Med. 2018;10:33.
Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1.
Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401-404.
Mullighan CG, Phillips LA, Su X, et al. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science. 2008;322:1377-1380.
Ding L, Ley TL, Larson DE, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012:481;506-510.<bib>
Anderson K, Lutz C, van Delft FW, et al. Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature. 2011:469:356-361.
van Delft FW, Horsley S, Colman S, et al. Clonal origins of relapse in ETV6-RUNX1 acute lymphoblastic leukemia. Blood. 2011:117:6247-6254.
Chen F, Kamradt M, Mulcahy M, et al. Caspase proteolysis of the cohesin component RAD21 promotes apoptosis. J Biol Chem. 2002;277:16775-16781.
Pati D, Zhang N, Plon SE. Linking sister chromatid cohesion and apoptosis: role of Rad21. Mol Cell Biol. 2002;22:8267-8277.
Zhang N, Jiang Y, Mao Q, et al. Characterization of the interaction between the cohesin subunits Rad21 and SA1/2. PLoS One. 2013;8:e69458.
Seitan VC, Hao B, Tachibana-Konwalski K, et al. A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation. Nature. 2011;476:467-471.
Thota S, Viny AD, Makishima H, et al. Genetic alterations of the cohesin complex genes in myeloid malignancies. Blood. 2014;124:1790-1798.
Hill VK, Kim J-S, Waldman T. Cohesin mutations in human cancer. Biochim Biophys Acta. 2016;1866:1-11. https://doi.org/10.1016/j.bbcan.2016.05.002
Fisher JB, McNulty M, Burke MJ, Crispino JD, Rao S. Cohesin mutations in myeloid malignancies. Trends Cancer Res. 2017;3:282-293.
Pang L, Liang Y, Pan J, Wang JR, Chai YH, Zhao WL. Clinical features and prognostic significance of TCF3-PBX1 fusion gene in Chinese children with acute lymphoblastic leukemia by using a modified ALL-BFM-95 protocol. Pediatr Hematol Oncol. 2015;32:173-181bib>
Felice MS, Gallego MS, Alonso CN, et al. Prognostic impact of t(1;19)/TCF3-PBX1 in childhood acute lymphoblastic leukemia in the context of Berlin-Frankfurt-Münster-based protocols. Leuk Lymphoma. 2011;52:1215-1221.
Kager L, Lion T, Attarbaschi A, et al. Incidence and outcome of TCF3-PBX1-positive acute lymphoblastic leukemia in Austrian children. Haematologica. 2007;92:1561-1564.
Irving JAE, Enshaei A, Parker CA, et al. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2016;128:911-922.
Antić Ž, Yu J, Van Reijmersdal SV, et al. Multiclonal complexity of pediatric acute lymphoblastic leukemia and the prognostic relevance of subclonal mutations. Haematologica. 2020. https://doi.org/10.3324/haematol.2020.259226
Jaffe JD, Wang Y, Chan HM, et al. Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nat Genet. 2013;45:1386-1391.
Ma X, Liu Y, Liu Y, et al. Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours. Nature. 2018;555:371-376.
Li B, Brady SW, Ma X, et al. Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia. Blood. 2020;135:41-55.
Antić Ž, Lelieveld SH, van der Ham CG, Sonneveld E, Hoogerbrugge PM, Kuiper RP. Unravelling the sequential interplay of mutational mechanisms during clonal evolution in relapsed pediatric acute lymphoblastic leukemia. Genes (Basel). 2021;12:214.
Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415-421.
Bercovich D, Ganmore I, Scott LM, et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet. 2008;372:1484-1492.
Kearney L, Gonzalez De Castro D, Yeung J, et al. Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia. Blood. 2009;113:646-648.
Mullighan CG, Zhang J, Harvey RC, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2009;106:9414-9418.
Yu CH, Chang WT, Jou ST, et al. TP53 alterations in relapsed childhood acute lymphoblastic leukemia. Cancer Sci. 2020;111:229-238.
Hof J, Krentz S, van Schewick C, et al. Mutations and deletions of the TP53 gene predict nonresponse to treatment and poor outcome in first relapse of childhood acute lymphoblastic leukemia. J Clin Oncol. 2011;29:3185-3193.
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;27:295-304.
Spinella J-F, Richer C, Cassart P, et al. Mutational dynamics of early and late relapsed childhood ALL: rapid clonal expansion and long-term dormancy. Blood Adv. 2018;2:177-188.
Schroeder MP, Bastian L, Eckert C, et al. Integrated analysis of relapsed B-cell precursor acute lymphoblastic leukemia identifies subtype-specific cytokine and metabolic signatures. Sci Rep. 2019;9:4188.
Takahashi H, Kajiwara R, Kato M, et al. Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Group (TCCSG) study L04-16. Int J Hematol. 2018;108:98-108.
Lin A, Cheng FWT, Chiang AKS, et al. Excellent outcome of acute lymphoblastic leukaemia with TCF3-PBX1 rearrangement in Hong Kong. Pediatr Blood Cancer. 2018;65:e27346.
Jeha S, Pei D, Raimondi SC, et al. Increased risk for CNS relapse in pre-B cell leukemia with the t(1;19)/TCF3-PBX1. Leukemia. 2009;23:1406-1409bib>
Moorman AV. New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia. Haematologica. 2016;101:407-416.
Pierro J, Saliba J, Narang S, et al. The NSD2 p.E1099K mutation is enriched at relapse and confers drug resistance in a cell context-dependent manner in pediatric acute lymphoblastic leukemia. Mol Cancer Res. 2020;18:1153-1165.
Buitenkamp TD, Izraeli S, Zimmermann M, et al. Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno Study Group. Blood. 2014;123:70-77.
Eckert C, Groeneveld-Krentz S, Kirschner-Schwabe R, et al. Improving stratification for children with late bone marrow B-cell acute lymphoblastic leukemia relapses with refined response classification and integration of genetics. J Clin Oncol. 2019;37:3493-3506.
Stengel A, Schnittger S, Weissmann S, et al. TP53 mutations occur in 15.7% of ALL and are associated with MYC-rearrangement, low hypodiploidy, and a poor prognosis. Blood. 2014;124:251-258.