DUX Hunting—Clinical Features and Diagnostic Challenges Associated with DUX4-Rearranged Leukaemia
Abstract
:Simple Summary
Abstract
1. Introduction
2. Description of the DUX4 Rearrangement
3. Disease Model
4. Genomic Landscape of DUX4r Leukaemia
5. Detecting DUX4r
6. Clinical Presentation
7. Prognosis and Treatment
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Inaba, H.; Greaves, M.; Mullighan, C.G. Acute lymphoblastic leukaemia. Lancet 2013, 381, 1943–1955. [Google Scholar] [CrossRef] [Green Version]
- Tasian, S.K.; Loh, M.L.; Hunger, S.P. Childhood acute lymphoblastic leukemia: Integrating genomics into therapy. Cancer 2015, 121, 3577–3590. [Google Scholar] [CrossRef] [PubMed]
- Hunger, S.P.; Mullighan, C.G. Redefining ALL classification: Toward detecting high-risk ALL and implementing precision medicine. Blood 2015, 125, 3977–3987. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harvey, R.C.; Mullighan, C.G.; Chen, I.-M.; Wharton, W.; Mikhail, F.M.; Carroll, A.J.; Kang, H.; Liu, W.; Dobbin, K.K.; Smith, M.A.; et al. Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Blood 2010, 115, 5312–5321. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mullighan, C.G.; Collins-Underwood, J.R.; Phillips, L.A.A.; Loudin, M.G.; Liu, W.; Zhang, J.; Ma, J.; Coustan-Smith, E.; Harvey, R.C.; Willman, C.L.; et al. Rearrangement of CRLF2 in B-progenitor-and Down syndrome-associated acute lymphoblastic leukemia. Nat. Genet. 2009, 41, 1243–1246. [Google Scholar] [CrossRef] [Green Version]
- Yeoh, E.-J.; Ross, M.E.; Shurtleff, S.A.; Williams, W.K.; Patel, D.; Mahfouz, R.; Behm, F.G.; Raimondi, S.C.; Relling, M.V.; Patel, A.; et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 2002, 1, 133–143. [Google Scholar] [CrossRef] [Green Version]
- Mullighan, C.G.; Miller, C.B.; Su, X.; Radtke, I.; Dalton, J.; Song, G.; Zhou, X.; Pui, C.-H.; Shurtleff, S.A.; Downing, J.R. ERG Deletions Define a Novel Subtype of B-Progenitor Acute Lymphoblastic Leukemia. Blood 2007, 110, 691. [Google Scholar] [CrossRef]
- Harvey, R.C.; Mullighan, C.G.; Wang, X.; Dobbin, K.K.; Davidson, G.S.; Bedrick, E.J.; Chen, I.-M.; Atlas, S.R.; Kang, H.; Ar, K.; et al. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: Correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome. Blood 2010, 116, 4874–4884. [Google Scholar] [CrossRef]
- Zhang, J.; McCastlain, K.; Yoshihara, H.; Xu, B.; Chang, Y.; Churchman, M.L.; Wu, G.; Li, Y.; Wei, L.; Iacobucci, I.; et al. Deregulation of DUX4 and ERG in acute lymphoblastic leukemia. Nat. Genet. 2016, 48, 1481–1489. [Google Scholar] [CrossRef]
- Zaliova, M.; Potuckova, E.; Hovorkova, L.; Musilova, A.; Winkowska, L.; Fiser, K.; Stuchly, J.; Mejstrikova, E.; Starkova, J.; Zuna, J.; et al. ERG deletions in childhood acute lymphoblastic leukemia with DUX4 rearrangements are mostly polyclonal, prognostically relevant and their detection rate strongly depends on screening method sensitivity. Haematologica 2019, 104, 1407–1416. [Google Scholar] [CrossRef] [Green Version]
- Potuckova, E.; Zuna, J.; Hovorkova, L.; Starkova, J.; Stary, J.; Trka, J.; Zaliova, M. Intragenic ERG Deletions Do Not Explain the Biology of ERG-Related Acute Lymphoblastic Leukemia. PLoS ONE 2016, 11, e0160385. [Google Scholar] [CrossRef] [PubMed]
- Yasuda, T.; Tsuzuki, S.; Kawazu, M.; Hayakawa, F.; Kojima, S.; Ueno, T.; Imoto, N.; Kohsaka, S.; Kunita, A.; Doi, K.; et al. Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults. Nat. Genet. 2016, 48, 569–574. [Google Scholar] [CrossRef] [PubMed]
- Lilljebjörn, H.; Henningsson, R.; Hyrenius-Wittsten, A.; Olsson, L.; Orsmark-Pietras, C.; von Palffy, S.; Askmyr, M.; Rissler, M.; Schrappe, M.; Cario, G.; et al. Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia. Nat. Commun. 2016, 7, 11790. [Google Scholar] [CrossRef] [PubMed]
- Zaliova, M.; Stuchly, J.; Winkowska, L.; Musilova, A.; Fiser, K.; Slamova, M.; Starkova, J.; Vaskova, M.; Hrusak, O.; Sramkova, L.; et al. Genomic landscape of pediatric B-other acute lymphoblastic leukemia in a consecutive European cohort. Haematologica 2019, 104, 1396–1406. [Google Scholar] [CrossRef] [PubMed]
- Marincevic-Zuniga, Y.; Dahlberg, J.; Nilsson, S.; Raine, A.; Nystedt, S.; Lindqvist, C.M.; Berglund, E.C.; Abrahamsson, J.; Cavelier, L.; Forestier, E.; et al. Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles. J. Hematol. Oncol. 2017, 10, 148. [Google Scholar] [CrossRef] [Green Version]
- Vendramini, E.; Giordan, M.; Giarin, E.; Michielotto, B.; Fazio, G.; Cazzaniga, G.; Biondi, A.; Silvestri, D.; Valsecchi, M.G.; Muckenthaler, M.U.; et al. High expression of miR-125b-2 and SNORD116 noncoding RNA clusters characterize ERG-related B cell precursor acute lymphoblastic leukemia. Oncotarget 2017, 8, 42398–42413. [Google Scholar] [CrossRef] [Green Version]
- Gu, Z.; Churchman, M.L.; Roberts, K.G.; Moore, I.; Zhou, X.; Nakitandwe, J.; Hagiwara, K.; Pelletier, S.; Gingras, S.; Berns, H.; et al. PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia. Nat. Genet. 2019, 51, 296–307. [Google Scholar] [CrossRef]
- Li, J.F.; Dai, Y.T.; Lilljebjörn, H.; Shen, S.H.; Cui, B.W.; Bai, L.; Liu, Y.F.; Qian, M.X.; Kubota, Y.; Kiyoi, H.; et al. Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases. Proc. Natl. Acad. Sci. USA 2018, 115, E11711–E11720. [Google Scholar] [CrossRef] [Green Version]
- Liu, Y.-F.; Wang, B.-Y.; Zhang, W.-N.; Huang, J.-Y.; Li, B.-S.; Zhang, M.; Jiang, L.; Li, J.-F.; Wang, M.-J.; Dai, Y.-J.; et al. Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia. EBioMedicine 2016, 8, 173–183. [Google Scholar] [CrossRef] [Green Version]
- Schroeder, M.P.; Bastian, L.; Eckert, C.; Gökbuget, N.; James, A.R.; Tanchez, J.O.; Schlee, C.; Isaakidis, K.; Häupl, B.; Baum, K.; et al. Integrated analysis of relapsed B-cell precursor Acute Lymphoblastic Leukemia identifies subtype-specific cytokine and metabolic signatures. Sci. Rep. 2019, 9, 4188. [Google Scholar] [CrossRef] [Green Version]
- James, A.R.; Schroeder, M.P.; Neumann, M.; Bastian, L.; Eckert, C.; Gökbuget, N.; Tanchez, J.O.; Schlee, C.; Isaakidis, K.; Schwartz, S.; et al. Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia. J. Hematol. Oncol. 2019, 12, 8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Winokur, S.T.; Bengtsson, U.; Feddersen, J.; Mathews, K.D.; Weiffenbach, B.; Bailey, H.; Markovich, R.P.; Murray, J.C.; Wasmuth, J.J.; Altherr, M.R. The DNA rearrangement associated with facioscapulohumeral muscular dystrophy involves a heterochromatin-associated repetitive element: Implications for a role of chromatin structure in the pathogenesis of the disease. Chromosome Res. 1994, 2, 225–234. [Google Scholar] [CrossRef] [PubMed]
- Cacurri, S.; Piazzo, N.; Deidda, G.; Vigneti, E.; Galluzzi, G.; Colantoni, L.; Merico, B.; Ricci, E.; Felicetti, L. Sequence homology between 4qter and 10qter loci facilitates the instability of subtelomeric KpnI repeat units implicated in facioscapulohumeral muscular dystrophy. Am. J. Hum. Genet. 1998, 63, 181–190. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- van Geel, M.; Dickson, M.C.; Beck, A.F.; Bolland, D.J.; Frants, R.R.; van der Maarel, S.M.; de Jong, P.J.; Hewitt, J.E. Genomic analysis of human chromosome 10q and 4q telomeres suggests a common origin. Genomics 2002, 79, 210–217. [Google Scholar] [CrossRef] [PubMed]
- van Deutekom, J.C.; Wijmenga, C.; van Tienhoven, E.A.; Gruter, A.M.; Hewitt, J.E.; Padberg, G.W.; van Ommen, G.J.; Hofker, M.H.; Frants, R.R. FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum. Mol. Genet. 1993, 2, 2037–2042. [Google Scholar] [CrossRef]
- Geng, L.N.; Yao, Z.; Snider, L.; Fong, A.P.; Cech, J.N.; Young, J.M.; van der Maarel, S.M.; Ruzzo, W.L.; Gentleman, R.C.; Tawil, R.; et al. DUX4 activates germline genes, retroelements, and immune mediators: Implications for facioscapulohumeral dystrophy. Dev. Cell 2012, 22, 38–51. [Google Scholar] [CrossRef] [Green Version]
- Snider, L.; Geng, L.N.; Lemmers, R.J.L.F.; Kyba, M.; Ware, C.B.; Nelson, A.M.; Tawil, R.; Filippova, G.N.; van der Maarel, S.M.; Tapscott, S.J.; et al. Facioscapulohumeral dystrophy: Incomplete suppression of a retrotransposed gene. PLoS Genet. 2010, 6, e1001181. [Google Scholar] [CrossRef] [Green Version]
- Gabriëls, J.; Beckers, M.C.; Ding, H.; De Vriese, A.; Plaisance, S.; van der Maarel, S.M.; Padberg, G.W.; Frants, R.R.; Hewitt, J.E.; Collen, D.; et al. Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element. Gene 1999, 236, 25–32. [Google Scholar] [CrossRef]
- Choi, S.H.; Gearhart, M.D.; Cui, Z.; Bosnakovski, D.; Kim, M.; Schennum, N.; Kyba, M. DUX4 recruits p300/CBP through its C-terminus and induces global H3K27 acetylation changes. Nucleic Acids Res. 2016, 44, 5161–5173. [Google Scholar] [CrossRef] [Green Version]
- Wijmenga, C.; Hewitt, J.E.; Sandkuijl, L.A.; Clark, L.N.; Wright, T.J.; Dauwerse, H.G.; Gruter, A.M.; Hofker, M.H.; Moerer, P.; Williamson, R. Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy. Nat. Genet. 1992, 2, 26–30. [Google Scholar] [CrossRef]
- Pandya, S.; King, W.M.; Tawil, R. Facioscapulohumeral dystrophy. Phys. Ther. 2008, 88, 105–113. [Google Scholar] [CrossRef] [PubMed]
- Zeng, W.; de Greef, J.C.; Chen, Y.-Y.; Chien, R.; Kong, X.; Gregson, H.C.; Winokur, S.T.; Pyle, A.; Robertson, K.D.; Schmiesing, J.A.; et al. Specific loss of histone H3 lysine 9 trimethylation and HP1gamma/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD). PLoS Genet. 2009, 5, e1000559. [Google Scholar] [CrossRef] [Green Version]
- van Overveld, P.G.M.; Lemmers, R.J.F.L.; Sandkuijl, L.A.; Enthoven, L.; Winokur, S.T.; Bakels, F.; Padberg, G.W.; van Ommen, G.-J.B.; Frants, R.R.; van der Maarel, S.M. Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy. Nat. Genet. 2003, 35, 315–317. [Google Scholar] [CrossRef]
- Lemmers, R.J.L.F.; van der Vliet, P.J.; Klooster, R.; Sacconi, S.; Camaño, P.; Dauwerse, J.G.; Snider, L.; Straasheijm, K.R.; van Ommen, G.J.; Padberg, G.W.; et al. A unifying genetic model for facioscapulohumeral muscular dystrophy. Science 2010, 329, 1650–1653. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dmitriev, P.; Kairov, U.; Robert, T.; Barat, A.; Lazar, V.; Carnac, G.; Laoudj-Chenivesse, D.; Vassetzky, Y.S. Cancer-related genes in the transcription signature of facioscapulohumeral dystrophy myoblasts and myotubes. J. Cell. Mol. Med. 2014, 18, 208–217. [Google Scholar] [CrossRef] [PubMed]
- Dib, C.; Zakharova, V.; Popova, E.; Kiseleva, E.; Chernyak, B.; Lipinski, M.; Vassetzky, Y.S. DUX4 Pathological Expression: Causes and Consequences in Cancer. Trends Cancer Res. 2019, 5, 268–271. [Google Scholar] [CrossRef]
- Kawamura-Saito, M.; Yamazaki, Y.; Kaneko, K.; Kawaguchi, N.; Kanda, H.; Mukai, H.; Gotoh, T.; Motoi, T.; Fukayama, M.; Aburatani, H.; et al. Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation. Hum. Mol. Genet. 2006, 15, 2125–2137. [Google Scholar] [CrossRef]
- Dyer, M.J.S.; Akasaka, T.; Capasso, M.; Dusanjh, P.; Lee, Y.F.; Karran, E.L.; Nagel, I.; Vater, I.; Cario, G.; Siebert, R. Immunoglobulin heavy chain locus chromosomal translocations in B-cell precursor acute lymphoblastic leukemia: Rare clinical curios or potent genetic drivers? Blood 2010, 115, 1490–1499. [Google Scholar] [CrossRef]
- Tian, L.; Shao, Y.; Nance, S.; Dang, J.; Xu, B.; Ma, X.; Li, Y.; Ju, B.; Dong, L.; Newman, S.; et al. Long-read sequencing unveils IGH-DUX4 translocation into the silenced IGH allele in B-cell acute lymphoblastic leukemia. Nat. Commun. 2019, 10, 2789. [Google Scholar] [CrossRef] [Green Version]
- Zur Stadt, U.; Alawi, M.; Adao, M.; Indenbirken, D.; Escherich, G.; Horstmann, M.A. Characterization of novel, recurrent genomic rearrangements as sensitive MRD targets in childhood B-cell precursor ALL. Blood Cancer J. 2019, 9, 96. [Google Scholar] [CrossRef]
- Kowaljow, V.; Marcowycz, A.; Ansseau, E.; Conde, C.B.; Sauvage, S.; Mattéotti, C.; Arias, C.; Corona, E.D.; Nuñez, N.G.; Leo, O.; et al. The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein. Neuromuscul. Disord. 2007, 17, 611–623. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tanaka, Y.; Kawazu, M.; Yasuda, T.; Tamura, M.; Hayakawa, F.; Kojima, S.; Ueno, T.; Kiyoi, H.; Naoe, T.; Mano, H. Transcriptional activities of DUX4 fusions in B-cell acute lymphoblastic leukemia. Haematologica 2018, 103, e522–e526. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dong, X.; Zhang, W.; Wu, H.; Huang, J.; Zhang, M.; Wang, P.; Zhang, H.; Chen, Z.; Chen, S.-J.; Meng, G. Structural basis of DUX4/IGH-driven transactivation. Leukemia 2018, 32, 1466–1476. [Google Scholar] [CrossRef] [PubMed]
- Mitsuhashi, H.; Ishimaru, S.; Homma, S.; Yu, B.; Honma, Y.; Beermann, M.L.; Miller, J.B. Functional domains of the FSHD-associated DUX4 protein. Biol. Open 2018, 7, bio033977. [Google Scholar] [CrossRef] [Green Version]
- Tsuzuki, S.; Taguchi, O.; Seto, M. Promotion and maintenance of leukemia by ERG. Blood 2011, 117, 3858–3868. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taoudi, S.; Bee, T.; Hilton, A.; Knezevic, K.; Scott, J.; Willson, T.A.; Collin, C.; Thomas, T.; Voss, A.K.; Kile, B.T.; et al. ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification. Genes Dev. 2011, 25, 251–262. [Google Scholar] [CrossRef] [Green Version]
- Clappier, E.; Auclerc, M.F.; Rapion, J.; Bakkus, M.; Caye, A.; Khemiri, A.; Giroux, C.; Hernandez, L.; Kabongo, E.; Savola, S.; et al. An intragenic ERG deletion is a marker of an oncogenic subtype of B-cell precursor acute lymphoblastic leukemia with a favorable outcome despite frequent IKZF1 deletions. Leukemia 2014, 28, 70–77. [Google Scholar] [CrossRef]
- Zaliova, M.; Zimmermannova, O.; Dörge, P.; Eckert, C.; Möricke, A.; Zimmermann, M.; Stuchly, J.; Teigler-Schlegel, A.; Meissner, B.; Koehler, R.; et al. ERG deletion is associated with CD2 and attenuates the negative impact of IKZF1 deletion in childhood acute lymphoblastic leukemia. Leukemia 2014, 28, 182–185. [Google Scholar] [CrossRef]
- Nibourel, O.; Guihard, S.; Roumier, C.; Pottier, N.; Terre, C.; Paquet, A.; Peyrouze, P.; Geffroy, S.; Quentin, S.; Alberdi, A.; et al. Copy-number analysis identified new prognostic marker in acute myeloid leukemia. Leukemia 2017, 31, 555–564. [Google Scholar] [CrossRef]
- Baldus, C.D.; Martus, P.; Burmeister, T.; Schwartz, S.; Gökbuget, N.; Bloomfield, C.D.; Hoelzer, D.; Thiel, E.; Hofmann, W.K. Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favorable outcome. J. Clin. Oncol. 2007, 25, 3739–3745. [Google Scholar] [CrossRef]
- Mullighan, C.G.; Miller, C.B.; Radtke, I.; Phillips, L.A.; Dalton, J.; Ma, J.; White, D.; Hughes, T.P.; Le Beau, M.M.; Pui, C.-H.; et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 2008, 453, 110–114. [Google Scholar] [CrossRef]
- Boer, J.M.; van der Veer, A.; Rizopoulos, D.; Fiocco, M.; Sonneveld, E.; de Groot-Kruseman, H.A.; Kuiper, R.P.; Hoogerbrugge, P.; Horstmann, M.; Zaliova, M.; et al. Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: An international collaborative study. Leukemia 2016, 30, 32–38. [Google Scholar] [CrossRef]
- Mullighan, C.G.; Su, X.; Zhang, J.; Radtke, I.; Phillips, L.A.A.; Miller, C.B.; Ma, J.; Liu, W.; Cheng, C.; Schulman, B.A.; et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N. Engl. J. Med. 2009, 360, 470–480. [Google Scholar] [CrossRef]
- Stanulla, M.; Dagdan, E.; Zaliova, M.; Möricke, A.; Palmi, C.; Cazzaniga, G.; Eckert, C.; Te Kronnie, G.; Bourquin, J.-P.; Bornhauser, B.; et al. IKZF1plus Defines a New Minimal Residual Disease-Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia. J. Clin. Oncol. 2018, 36, 1240–1249. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Slamova, L.; Starkova, J.; Fronkova, E.; Zaliova, M.; Reznickova, L.; van Delft, F.W.; Vodickova, E.; Volejnikova, J.; Zemanova, Z.; Polgarova, K.; et al. CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage. Leukemia 2014, 28, 609–620. [Google Scholar] [CrossRef] [PubMed]
- Akkari, Y.M.N.; Bruyere, H.; Hagelstrom, R.T.; Kanagal-Shamanna, R.; Liu, J.; Luo, M.; Mikhail, F.M.; Pitel, B.A.; Raca, G.; Shago, M.; et al. Evidence-based review of genomic aberrations in B-lymphoblastic leukemia/lymphoma: Report from the cancer genomics consortium working group for lymphoblastic leukemia. Cancer Genet. 2020, 243, 52–72. [Google Scholar] [CrossRef] [PubMed]
- Harrison, C.J.; Moorman, A.V.; Barber, K.E.; Broadfield, Z.J.; Cheung, K.L.; Harris, R.L.; Jalali, G.R.; Robinson, H.M.; Strefford, J.C.; Stewart, A.; et al. Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia: A UK Cancer Cytogenetics Group Study. Br. J. Haematol. 2005, 129, 520–530. [Google Scholar] [CrossRef]
- Russell, L.J.; Capasso, M.; Vater, I.; Akasaka, T.; Bernard, O.A.; Calasanz, M.J.; Chandrasekaran, T.; Chapiro, E.; Gesk, S.; Griffiths, M.; et al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood 2009, 114, 2688–2698. [Google Scholar] [CrossRef]
- Hewitt, J.E.; Lyle, R.; Clark, L.N.; Valleley, E.M.; Wright, T.J.; Wijmenga, C.; van Deutekom, J.C.; Francis, F.; Sharpe, P.T.; Hofker, M. Analysis of the tandem repeat locus D4Z4 associated with facioscapulohumeral muscular dystrophy. Hum. Mol. Genet. 1994, 3, 1287–1295. [Google Scholar] [CrossRef]
- Ohki, K.; Takahashi, H.; Fukushima, T.; Nanmoku, T.; Kusano, S.; Mori, M.; Nakazawa, Y.; Yuza, Y.; Migita, M.; Okuno, H.; et al. Impact of immunophenotypic characteristics on genetic subgrouping in childhood acute lymphoblastic leukemia: Tokyo Children’s Cancer Study Group (TCCSG) study L04-16. Genes Chromosomes Cancer 2020, 59, 551–561. [Google Scholar] [CrossRef]
- Tasian, S.K.; Doral, M.Y.; Borowitz, M.J.; Wood, B.L.; Chen, I.-M.; Harvey, R.C.; Gastier-Foster, J.M.; Willman, C.L.; Hunger, S.P.; Mullighan, C.G.; et al. Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia. Blood 2012, 120, 833–842. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schinnerl, D.; Mejstrikova, E.; Schumich, A.; Zaliova, M.; Fortschegger, K.; Nebral, K.; Attarbaschi, A.; Fiser, K.; Kauer, M.O.; Popitsch, N.; et al. CD371 cell surface expression: A unique feature of DUX4-rearranged acute lymphoblastic leukemia. Haematologica 2019, 104, e352–e355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Novakova, M.; Vakrmanova, B.; Slamova, L.; Musilova, A.; Brüggemann, M.; Ritgen, M.; Fronkova, E.; Kalina, T.; Trka, J.; Stary, J.; et al. Switching Towards Monocytic Lineage and Discordancy between Flow Cytometric and PCR Minimal Residual Disease Results Is a Hallmark Feature of DUX4 Rearranged B-Cell Precursor Acute Lymphoblastic Leukemia. Blood 2018, 132, 2825. [Google Scholar] [CrossRef]
- Nicorici, D.; Şatalan, M.; Edgren, H.; Kangaspeska, S.; Murumägi, A.; Kallioniemi, O.; Virtanen, S.; Kilkku, O. FusionCatcher—A tool for finding somatic fusion genes in paired-end RNA-sequencing data. bioRxiv 2014, 011650. [Google Scholar]
- Kim, D.; Salzberg, S.L. TopHat-Fusion: An algorithm for discovery of novel fusion transcripts. Genome Biol. 2011, 12, R72. [Google Scholar] [CrossRef] [Green Version]
- McPherson, A.; Hormozdiari, F.; Zayed, A.; Giuliany, R.; Ha, G.; Sun, M.G.F.; Griffith, M.; Heravi Moussavi, A.; Senz, J.; Melnyk, N.; et al. deFuse: An algorithm for gene fusion discovery in tumor RNA-Seq data. PLoS Comput. Biol. 2011, 7, e1001138. [Google Scholar] [CrossRef]
- Tian, L.; Li, Y.; Edmonson, M.N.; Zhou, X.; Newman, S.; McLeod, C.; Thrasher, A.; Liu, Y.; Tang, B.; Rusch, M.C.; et al. CICERO: A versatile method for detecting complex and diverse driver fusions using cancer RNA sequencing data. Genome Biol. 2020, 21, 126. [Google Scholar] [CrossRef]
- Brown, L.M.; Lonsdale, A.; Zhu, A.; Davidson, N.M.; Schmidt, B.; Hawkins, A.; Wallach, E.; Martin, M.; Mechinaud, F.M.; Khaw, S.L.; et al. The application of RNA sequencing for the diagnosis and genomic classification of pediatric acute lymphoblastic leukemia. Blood Adv. 2020, 4, 930–942. [Google Scholar] [CrossRef]
- Jerchel, I.S.; Chatzivasileiou, D.; Hoogkamer, A.Q.; Boer, J.M.; Beverloo, H.B.; Pieters, R.; den Boer, M.L. High PDGFRA expression does not serve as an effective therapeutic target in ERG-deleted B-cell precursor acute lymphoblastic leukemia. Haematologica 2018, 103, e73–e77. [Google Scholar] [CrossRef] [Green Version]
- Roberts, K.G.; Li, Y.; Payne-Turner, D.; Harvey, R.C.; Yang, Y.-L.; Pei, D.; McCastlain, K.; Ding, L.; Lu, C.; Song, G.; et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N. Engl. J. Med. 2014, 371, 1005–1015. [Google Scholar] [CrossRef] [Green Version]
- Dong, X.; Zhang, H.; Cheng, N.; Li, K.; Meng, G. DUX4HD2-DNAERG structure reveals new insight into DUX4-Responsive-Element. Leukemia 2019, 33, 550–553. [Google Scholar] [CrossRef]
- Salome’, M.; Caronni, C.; Runfola, V.; Giambruno, R.; Campolungo, D.; Ghirardi, C.; Gabellini, D. PB1661 Characterization of a DUX4-IGH inhibitor as a possible treatment for acute lymphoblastic leukemia. HemaSphere 2019, 3, 768. [Google Scholar] [CrossRef]
Reference | Detection Method | Cohort (Age Range in Years) | Frequency DUX4r | Additional Alterations | Prognosis | |||
---|---|---|---|---|---|---|---|---|
ERG | IKZF1 | PAX5 | CDKN2A | |||||
Yeoh et al. 2002; [6] | Microarray GEP | Paediatric ALL (<19) | 14/327 (4.3%) | — | — | — | — | — |
Mullighan et al. 2007; [7] | Microarray GEP | B-ALL | 19/218 (8.7%) | 13/19 (68.4%) | — | — | — | — |
Harvey et al. 2010; [8] | Microarray GEP | HR * B-ALL (1–20) | 21/207 (10.1%) | 8/21 (38.1%) | 6/21 (28.6%) | 3/21 (14.3%) | 5/21 (23.8%) | 4-yr RFS 94% ± 5.1 |
HR * B-ALL (validation cohort) | 5/99 (5.1%) | — | — | — | — | 1/5 (20%) relapse | ||
Zhang et al. 2016; [9] | Microarray GEP RNA-seq (n=175) | Paediatric B-ALL (0–15) | 94/1347 (7.0%) | 54/91 (59.3%) | 17/91 (18.7%) | 3/91 (3.3%) | — | — |
Adolescent B-ALL (16–20) | 38/395 (9.62%) | 23/38 (60.5%) | 19/38 (50%) | 6/38 (15.8%) | — | — | ||
Young Adult B-ALL (21–39) | 9/171 (5.3%) | 3/9 (33.3%) | 3/9 (33.3%) | 2/9 (22.2%) | — | — | ||
Yasuda et al. 2016; [12] | RNA-seq | AYA Ph-negative B-ALL (15–39) | 12/62 (19.4%) | — | — | — | — | 8 CR; 1 CR after SCT; 1 Early mortality; 2 NA |
Lilljebjörn et al. 2016; [13] | RNA-seq | Paediatric B-ALL (<18) | 8/195 (4%) | 5/8 (62.5%) | — | — | — | No observed relapses |
Paediatric B-Other ^ (2–15) | 20/49 (40.8%) | 10/20 (50%) | — | — | — | 4/20 (20%) relapse | ||
Liu et al. 2016; [19] | RNA-seq | Children (<18) | 6/94 (6.4%) | — | 3/6 (50%) | 4/6 (66.7%) | 3/6 (50%) | 5-yr OS 100% |
Adult (>18) | 5/78 (6.4%) | — | 1/5 (20%) | 3/5 (60%) | 3/5 (60%) | 5-yr OS 53% | ||
Vendramini 2017; [16] | Microarray GEP | Paediatric B-Other ^ (<18) | 35/143 (24.5%) | 14/34 (41.2%) | 12/34 (35.3%) | 4/34 (11.8%) | 5/34 (14.7%) | 5-yr EFS 91.1% 4.9 |
Marincevic-Zuniga 2017 [15] | RNA-seq | Paediatric B-ALL (<18) | 9/116 (7.8%) | 7/9 (77.8%) | — | — | — | 1/9 (11.1%) relapses |
Li et al. 2018; [18] | RNA-seq | Children (<18) | 50/906 (5.5%) | — | — | — | — | — |
Adult (>18) | 13/258 (5.0%) | — | — | — | — | — | ||
Zur Stadt et al. 2019; [40] | gc-HTS | B-ALL (excludes ETV6-RUNX1, KMT2Ar and Ph+ALL) | 10/164 (6.1%) | 2/10 (20%) | — | — | — | — |
Zaliova et al. 2019; [14] | RNA-seq | Paediatric B-Other ^ (1–18) | 30/110 (27%) | 19/30 (63%) | 6/30 (20%) | 6/30 (20%) | 9/30 (30%) | — |
Gu et al. 2019; [17] | RNA-seq | Paediatric (0.2–15) | 61/1191 (5.1%) | — | 2/35 (5.7%) | — | — | Child (<18) 5-yr EFS and OS 93.2% ± 3.8 Adult (>18) 5-yr EFS 84.6% ± 10; 5-yr OS 85.7% ± 9.4 |
AYA B-ALL (16–39) | 33/419 (7.9%) | — | 3/18 (16.7%) | — | — | |||
Adult B-ALL (40–79) | 12/378 (3.2%) | — | — | — | — |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Rehn, J.A.; O'Connor, M.J.; White, D.L.; Yeung, D.T. DUX Hunting—Clinical Features and Diagnostic Challenges Associated with DUX4-Rearranged Leukaemia. Cancers 2020, 12, 2815. https://doi.org/10.3390/cancers12102815
Rehn JA, O'Connor MJ, White DL, Yeung DT. DUX Hunting—Clinical Features and Diagnostic Challenges Associated with DUX4-Rearranged Leukaemia. Cancers. 2020; 12(10):2815. https://doi.org/10.3390/cancers12102815
Chicago/Turabian StyleRehn, Jacqueline A., Matthew J. O'Connor, Deborah L. White, and David T. Yeung. 2020. "DUX Hunting—Clinical Features and Diagnostic Challenges Associated with DUX4-Rearranged Leukaemia" Cancers 12, no. 10: 2815. https://doi.org/10.3390/cancers12102815