Literature DB >> 31719049

Comprehensive Transcriptome Profiling of Cryptic CBFA2T3-GLIS2 Fusion-Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study.

Jenny L Smith1, Rhonda E Ries2, Tiffany Hylkema2, Todd A Alonzo3,4,5, Robert B Gerbing3, Marianne T Santaguida6, Lisa Eidenschink Brodersen7, Laura Pardo2,7, Carrie L Cummings2, Keith R Loeb2, Quy Le2, Suzan Imren2, Amanda R Leonti2, Alan S Gamis8, Richard Aplenc9, E Anders Kolb10, Jason E Farrar11, Timothy J Triche12, Cu Nguyen13, Daoud Meerzaman13, Michael R Loken7, Vivian G Oehler2, Hamid Bolouri14, Soheil Meshinchi1,3,15.   

Abstract

PURPOSE: A cryptic inv(16)(p13.3q24.3) encoding the CBFA2T3-GLIS2 fusion is associated with poor outcome in infants with acute megakaryocytic leukemia. We aimed to broaden our understanding of the pathogenesis of this fusion through transcriptome profiling. EXPERIMENTAL
DESIGN: Available RNA from children and young adults with de novo acute myeloid leukemia (AML; N = 1,049) underwent transcriptome sequencing (mRNA and miRNA). Transcriptome profiles for those with the CBFA2T3-GLIS2 fusion (N = 24) and without (N = 1,025) were contrasted to define fusion-specific miRNAs, genes, and pathways. Clinical annotations defined distinct fusion-associated disease characteristics and outcomes.
RESULTS: The CBFA2T3-GLIS2 fusion was restricted to infants <3 years old (P < 0.001), and the presence of this fusion was highly associated with adverse outcome (P < 0.001) across all morphologic classifications. Further, there was a striking paucity of recurrent cooperating mutations, and transduction of cord blood stem cells with this fusion was sufficient for malignant transformation. CBFA2T3-GLIS2 positive cases displayed marked upregulation of genes with cell membrane/extracellular matrix localization potential, including NCAM1 and GABRE. Additionally, miRNA profiling revealed significant overexpression of mature miR-224 and miR-452, which are intronic miRNAs transcribed from the GABRE locus. Gene-set enrichment identified dysregulated Hippo, TGFβ, and hedgehog signaling, as well as NCAM1 (CD56) interaction pathways. Therapeutic targeting of fusion-positive leukemic cells with CD56-directed antibody-drug conjugate caused significant cytotoxicity in leukemic blasts.
CONCLUSIONS: The CBFA2T3-GLIS2 fusion defines a highly refractory entity limited to infants that appears to be sufficient for malignant transformation. Transcriptome profiling elucidated several highly targetable genes and pathways, including the identification of CD56, providing a highly plausible target for therapeutic intervention. ©2019 American Association for Cancer Research.

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Year:  2019        PMID： 31719049      PMCID： PMC7002196          DOI： 10.1158/1078-0432.CCR-19-1800

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   12.531


  48 in total

1.  De novo assembly and analysis of RNA-seq data.

Authors:  Gordon Robertson; Jacqueline Schein; Readman Chiu; Richard Corbett; Matthew Field; Shaun D Jackman; Karen Mungall; Sam Lee; Hisanaga Mark Okada; Jenny Q Qian; Malachi Griffith; Anthony Raymond; Nina Thiessen; Timothee Cezard; Yaron S Butterfield; Richard Newsome; Simon K Chan; Rong She; Richard Varhol; Baljit Kamoh; Anna-Liisa Prabhu; Angela Tam; YongJun Zhao; Richard A Moore; Martin Hirst; Marco A Marra; Steven J M Jones; Pamela A Hoodless; Inanc Birol
Journal:  Nat Methods       Date:  2010-10-10       Impact factor: 28.547

2.  AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia: a report from the Children's Oncology Group.

Authors:  Todd M Cooper; Janet Franklin; Robert B Gerbing; Todd A Alonzo; Craig Hurwitz; Susana C Raimondi; Betsy Hirsch; Franklin O Smith; Prasad Mathew; Robert J Arceci; James Feusner; Robert Iannone; Robert S Lavey; Soheil Meshinchi; Alan Gamis
Journal:  Cancer       Date:  2011-07-15       Impact factor: 6.860

3.  The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions.

Authors:  Hamid Bolouri; Jason E Farrar; Timothy Triche; Rhonda E Ries; Emilia L Lim; Todd A Alonzo; Yussanne Ma; Richard Moore; Andrew J Mungall; Marco A Marra; Jinghui Zhang; Xiaotu Ma; Yu Liu; Yanling Liu; Jaime M Guidry Auvil; Tanja M Davidsen; Patee Gesuwan; Leandro C Hermida; Bodour Salhia; Stephen Capone; Giridharan Ramsingh; Christian Michel Zwaan; Sanne Noort; Stephen R Piccolo; E Anders Kolb; Alan S Gamis; Malcolm A Smith; Daniela S Gerhard; Soheil Meshinchi
Journal:  Nat Med       Date:  2017-12-11       Impact factor: 53.440

4.  ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia.

Authors:  Cécile Thirant; Cathy Ignacimouttou; Cécile K Lopez; M'Boyba Diop; Lou Le Mouël; Clarisse Thiollier; Aurélie Siret; Phillipe Dessen; Zakia Aid; Julie Rivière; Philippe Rameau; Céline Lefebvre; Mehdi Khaled; Guy Leverger; Paola Ballerini; Arnaud Petit; Hana Raslova; Catherine L Carmichael; Benjamin T Kile; Eric Soler; John D Crispino; Christian Wichmann; Françoise Pflumio; Jürg Schwaller; William Vainchenker; Camille Lobry; Nathalie Droin; Olivier A Bernard; Sébastien Malinge; Thomas Mercher
Journal:  Cancer Cell       Date:  2017-03-13       Impact factor: 31.743

5.  Outcomes in CCG-2961, a children's oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children's oncology group.

Authors:  Beverly J Lange; Franklin O Smith; James Feusner; Dorothy R Barnard; Patricia Dinndorf; Stephen Feig; Nyla A Heerema; Carola Arndt; Robert J Arceci; Nita Seibel; Margie Weiman; Kathryn Dusenbery; Kevin Shannon; Sandra Luna-Fineman; Robert B Gerbing; Todd A Alonzo
Journal:  Blood       Date:  2007-11-13       Impact factor: 22.113

6.  Lorvotuzumab mertansine, a CD56-targeting antibody-drug conjugate with potent antitumor activity against small cell lung cancer in human xenograft models.

Authors:  Kathleen R Whiteman; Holly A Johnson; Michele F Mayo; Charlene A Audette; Christina N Carrigan; Alyssa LaBelle; Lawrence Zukerberg; John M Lambert; Robert J Lutz
Journal:  MAbs       Date:  2014-01-08       Impact factor: 5.857

7.  Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study.

Authors:  Jasmijn D E de Rooij; Riccardo Masetti; Marry M van den Heuvel-Eibrink; Jean-Michel Cayuela; Jan Trka; Dirk Reinhardt; Mareike Rasche; Edwin Sonneveld; Todd A Alonzo; Maarten Fornerod; Martin Zimmermann; Martina Pigazzi; Rob Pieters; Soheil Meshinchi; C Michel Zwaan; Franco Locatelli
Journal:  Blood       Date:  2016-04-25       Impact factor: 22.113

8.  Regulation of ITGA3 by the anti-tumor miR-199 family inhibits cancer cell migration and invasion in head and neck cancer.

Authors:  Keiichi Koshizuka; Toyoyuki Hanazawa; Naoko Kikkawa; Takayuki Arai; Atsushi Okato; Akira Kurozumi; Mayuko Kato; Koji Katada; Yoshitaka Okamoto; Naohiko Seki
Journal:  Cancer Sci       Date:  2017-07-04       Impact factor: 6.716

9.  Integrated epigenetic and genetic analysis identifies markers of prognostic significance in pediatric acute myeloid leukemia.

Authors:  Jatinder K Lamba; Xueyuan Cao; Susana C Raimondi; Roya Rafiee; James R Downing; Shi Lei; Tanja Gruber; Raul C Ribeiro; Jeffrey E Rubnitz; Stanley B Pounds
Journal:  Oncotarget       Date:  2018-06-01

10.  miR-133a function in the pathogenesis of dedifferentiated liposarcoma.

Authors:  Peter Y Yu; Gonzalo Lopez; Danielle Braggio; David Koller; Kate Lynn J Bill; Bethany C Prudner; Abbie Zewdu; James L Chen; O Hans Iwenofu; Dina Lev; Anne M Strohecker; Joelle M Fenger; Raphael E Pollock; Denis C Guttridge
Journal:  Cancer Cell Int       Date:  2018-06-26       Impact factor: 5.722
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  12 in total

1.  Bortezomib is significantly beneficial for de novo pediatric AML patients with low phosphorylation of the NF-κB subunit RelA.

Authors:  Anneke D van Dijk; Fieke W Hoff; Yihua Qiu; Robert B Gerbing; Alan S Gamis; Richard Aplenc; E Anders Kolb; Todd A Alonzo; Soheil Meshinchi; Gaye N Jenkins; Eveline S J M de Bont; Steven M Kornblau; Terzah M Horton
Journal:  Proteomics Clin Appl       Date:  2021-11-17       Impact factor: 3.603

Review 2.  GLIS1-3: Links to Primary Cilium, Reprogramming, Stem Cell Renewal, and Disease.

Authors:  Anton M Jetten; David W Scoville; Hong Soon Kang
Journal:  Cells       Date:  2022-06-03       Impact factor: 7.666

Review 3.  Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.

Authors:  Shannon E Conneely; Alexandra M Stevens
Journal:  Curr Oncol Rep       Date:  2021-01-13       Impact factor: 5.075

4.  Molecular Classification and Tumor Microenvironment Characterization of Gallbladder Cancer by Comprehensive Genomic and Transcriptomic Analysis.

Authors:  Nobutaka Ebata; Masashi Fujita; Shota Sasagawa; Kazuhiro Maejima; Yuki Okawa; Yutaka Hatanaka; Tomoko Mitsuhashi; Ayako Oosawa-Tatsuguchi; Hiroko Tanaka; Satoru Miyano; Toru Nakamura; Satoshi Hirano; Hidewaki Nakagawa
Journal:  Cancers (Basel)       Date:  2021-02-10       Impact factor: 6.639

5.  Revealing the intratumoral heterogeneity of non-DS acute megakaryoblastic leukemia in single-cell resolution.

Authors:  Narun Su; Zifeng Li; Jiapeng Yang; Yang Fu; Xiaohua Zhu; Hui Miao; Yi Yu; Wenjin Jiang; Jun Le; Xiaowen Qian; Hongsheng Wang; Maoxiang Qian; Xiaowen Zhai
Journal:  Front Oncol       Date:  2022-08-08       Impact factor: 5.738

6.  Integrated stem cell signature and cytomolecular risk determination in pediatric acute myeloid leukemia.

Authors:  Benjamin J Huang; Jenny L Smith; Jason E Farrar; Yi-Cheng Wang; Masayuki Umeda; Rhonda E Ries; Amanda R Leonti; Erin Crowgey; Scott N Furlan; Katherine Tarlock; Marcos Armendariz; Yanling Liu; Timothy I Shaw; Lisa Wei; Robert B Gerbing; Todd M Cooper; Alan S Gamis; Richard Aplenc; E Anders Kolb; Jeffrey Rubnitz; Jing Ma; Jeffery M Klco; Xiaotu Ma; Todd A Alonzo; Timothy Triche; Soheil Meshinchi
Journal:  Nat Commun       Date:  2022-09-19       Impact factor: 17.694

7.  Heat shock factor 1 (HSF1-pSer326) predicts response to bortezomib-containing chemotherapy in pediatric AML: a COG report.

Authors:  Fieke W Hoff; Anneke D van Dijk; Yihua Qiu; Peter P Ruvolo; Robert B Gerbing; Amanda R Leonti; Gaye N Jenkins; Alan S Gamis; Richard Aplenc; E Anders Kolb; Todd A Alonzo; Soheil Meshinchi; Eveline S J M de Bont; Sophia W M Bruggeman; Steven M Kornblau; Terzah M Horton
Journal:  Blood       Date:  2021-02-25       Impact factor: 22.113

8.  What Is Abnormal in Normal Karyotype Acute Myeloid Leukemia in Children? Analysis of the Mutational Landscape and Prognosis of the TARGET-AML Cohort.

Authors:  Morten Krogh Herlin; Sara A Yones; Eigil Kjeldsen; Linda Holmfeldt; Henrik Hasle
Journal:  Genes (Basel)       Date:  2021-05-21       Impact factor: 4.096

Review 9.  Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge.

Authors:  Julie Quessada; Wendy Cuccuini; Paul Saultier; Marie Loosveld; Christine J Harrison; Marina Lafage-Pochitaloff
Journal:  Genes (Basel)       Date:  2021-06-17       Impact factor: 4.141

Review 10.  Insights into the molecular profiles of adult and paediatric acute myeloid leukaemia.

Authors:  Myint Myat Khine Aung; Megan L Mills; Joana Bittencourt-Silvestre; Karen Keeshan
Journal:  Mol Oncol       Date:  2021-02-11       Impact factor: 6.603
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