CREBBP Alterations are Associated with A Poor Prognosis in de novo AML

Letter to Blood| April 27, 2023 CREBBP alterations are associated with a poor prognosis in de novo AML Adam J. Lamble, Adam J. Lamble 1Division of Hematology and Oncology, Seattle Children's Hospital, Seattle, WA Search for other works by this author on: This Site PubMed Google Scholar Kohei Hagiwara, Kohei Hagiwara 2Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN Search for other works by this author on: This Site PubMed Google Scholar Robert B. Gerbing, Robert B. Gerbing 3Children's Oncology Group, Monrovia, CA Search for other works by this author on: This Site PubMed Google Scholar Jenny L. Smith, Jenny L. Smith 4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA Search for other works by this author on: This Site PubMed Google Scholar Pandurang Kolekar, Pandurang Kolekar 2Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN https://orcid.org/0000-0003-0044-0076 Search for other works by this author on: This Site PubMed Google Scholar Rhonda E. Ries, Rhonda E. Ries 4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA Search for other works by this author on: This Site PubMed Google Scholar Edward A. Kolb, Edward A. Kolb 5Division of Oncology, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE Search for other works by this author on: This Site PubMed Google Scholar Todd A. Alonzo, Todd A. Alonzo 3Children's Oncology Group, Monrovia, CA6Keck School of Medicine, University of Southern California, Los Angeles, CA Search for other works by this author on: This Site PubMed Google Scholar Xiaotu Ma, Xiaotu Ma 2Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN Search for other works by this author on: This Site PubMed Google Scholar Soheil Meshinchi Soheil Meshinchi 4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA Search for other works by this author on: This Site PubMed Google Scholar Blood (2023) 141 (17): 2156–2159. https://doi.org/10.1182/blood.2022017545 Article history Submitted: June 24, 2022 Accepted: January 4, 2023 First Edition: January 12, 2023 Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Adam J. Lamble, Kohei Hagiwara, Robert B. Gerbing, Jenny L. Smith, Pandurang Kolekar, Rhonda E. Ries, Edward A. Kolb, Todd A. Alonzo, Xiaotu Ma, Soheil Meshinchi; CREBBP alterations are associated with a poor prognosis in de novo AML. Blood 2023; 141 (17): 2156–2159. doi: https://doi.org/10.1182/blood.2022017545 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search Subjects: Myeloid Neoplasia, Pediatric Hematology TO THE EDITOR: The cyclic adenosine monophosphate response element-binding protein (CREBBP) gene is located on chromosome 16p13 and encodes a histone acetyltransferase having the same name that is involved in transcriptional regulation and cell cycle control.1,2 The translocation t(8;16)(p11;p13)[KAT6A::CREBBP] results in the disruption of CREBBP as well as its fusion to KAT6A, another gene important in transcription control. This fusion is sufficient for leukemogenesis and leads to a rare but well described type of acute myeloid leukemia (AML) with consistent biologic characteristics and a distinct gene expression profile.3-8 Although generally associated with inferior outcomes among adults, including a recent adjustment made by the European LeukemiaNet toward the adverse-risk group, there are variable reports regarding the prognostic significance of this fusion among pediatric patients.4,7,9 This prognostic variability is partially... References 1.Chan HM, La Thangue NB. p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci. 2001;114(Pt 13):2363-2373.Google Scholar 2.Shiama N. The p300/CBP family: integrating signals with transcription factors and chromatin. Trends Cell Biol. 1997;7(6):230-236.Google ScholarCrossrefSearch ADS PubMed 3.Camos M, Esteve J, Jares P, et al. Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression. Cancer Res. 2006;66(14):6947-6954.Google ScholarCrossrefSearch ADS PubMed 4.Coenen EA, Zwaan CM, Reinhardt D, et al. Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Munster AML-study group. Blood. 2013;122(15):2704-2713.Google ScholarCrossrefSearch ADS PubMed 5.Diaz-Beya M, Navarro A, Ferrer G, et al. Acute myeloid leukemia with translocation (8;16)(p11;p13) and MYST3-CREBBP rearrangement harbors a distinctive microRNA signature targeting RET proto-oncogene. Leukemia. 2013;27(3):595-603.Google ScholarCrossrefSearch ADS PubMed 6.Gervais C, Murati A, Helias C, et al. Acute myeloid leukaemia with 8p11 (MYST3) rearrangement: an integrated cytologic, cytogenetic and molecular study by the groupe francophone de cytogenetique hematologique. Leukemia. 2008;22(8):1567-1575.Google ScholarCrossrefSearch ADS PubMed 7.Haferlach T, Kohlmann A, Klein HU, et al. AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features. Leukemia. 2009;23(5):934-943.Google ScholarCrossrefSearch ADS PubMed 8.Xie W, Hu S, Xu J, Chen Z, Medeiros LJ, Tang G. Acute myeloid leukemia with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP in adults. Ann Hematol. 2019;98(5):1149-1157.Google ScholarCrossrefSearch ADS PubMed 9.Dohner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377.Google ScholarCrossrefSearch ADS PubMed 10.Barrett R, Morash B, Roback D, et al. FISH identifies a KAT6A/CREBBP fusion caused by a cryptic insertional t(8;16) in a case of spontaneously remitting congenital acute myeloid leukemia with a normal karyotype. Pediatr Blood Cancer. 2017;64(8):e26450.Google ScholarCrossrefSearch ADS 11.Classen CF, Behnisch W, Reinhardt D, Koenig M, Moller P, Debatin KM. Spontaneous complete and sustained remission of a rearrangement CBP (16p13)-positive disseminated congenital myelosarcoma. Ann Hematol. 2005;84(4):274-275.Google ScholarCrossrefSearch ADS PubMed 12.Dinulos JG, Hawkins DS, Clark BS, Francis JS. Spontaneous remission of congenital leukemia. J Pediatr. 1997;131(2):300-303.Google ScholarCrossrefSearch ADS 13.Hanada T, Ono I, Minosaki Y, Moriyama N, Nakahara S, Ohtsu A. Translocation t(8;16)(p11;p13) in neonatal acute monocytic leukaemia. Eur J Pediatr. 1991;150(5):323-324.Google ScholarCrossrefSearch ADS PubMed 14.Liu M, Ren Y, Wang X, et al. Two rare cases of acute myeloid leukemia with t(8;16)(p11.2;p13.3) and 1q duplication: case presentation and literature review. Mol Cytogenet. 2020;13(1):1-9.Google ScholarCrossrefSearch ADS PubMed 15.Wong KF, Yuen HL, Siu LL, Pang A, Kwong YL. t(8;16)(p11;p13) predisposes to a transient but potentially recurring neonatal leukemia. Hum Pathol. 2008;39(11):1702-1707.Google ScholarCrossrefSearch ADS PubMed 16.Wu X, Sulavik D, Roulston D, Lim MS. Spontaneous remission of congenital acute myeloid leukemia with t(8;16)(p11;13). Pediatr Blood Cancer. 2011;56(2):331-332.Google ScholarCrossrefSearch ADS PubMed 17.Andrade FG, Noronha EP, Baseggio RM, et al. Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis. Rev Bras Hematol Hemoter. 2016;38(4):291-297.Google ScholarCrossrefSearch ADS PubMed 18.Hagiwara K, Ding L, Edmonson MN, et al. RNAIndel: discovering somatic coding indels from tumor RNA-Seq data. Bioinformatics. 2020;36(5):1382-1390.Google ScholarCrossrefSearch ADS PubMed 19.Cancer Genome Atlas Research N, Ley TJ, Miller C, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059-2074.Google ScholarCrossrefSearch ADS 20.Tyner JW, Tognon CE, Bottomly D, et al. Functional genomic landscape of acute myeloid leukaemia. Nature. 2018;562(7728):526-531.Google ScholarCrossrefSearch ADS PubMed 21.Ross ME, Mahfouz R, Onciu M, et al. Gene expression profiling of pediatric acute myelogenous leukemia. Blood. 2004;104(12):3679-3687.Google ScholarCrossrefSearch ADS PubMed 22.Hellwig M, Merk DJ, Lutz B, Schuller U. Preferential sensitivity to HDAC inhibitors in tumors with CREBBP mutation. Cancer Gene Ther. 2020;27(5):294-300.Google ScholarCrossrefSearch ADS PubMed 23.Mondello P, Tadros S, Teater M, et al. Selective inhibition of HDAC3 targets synthetic vulnerabilities and activates immune surveillance in lymphoma. Cancer Discov. 2020;10(3):440-459.Google ScholarCrossrefSearch ADS PubMed © 2023 by The American Society of Hematology2023 © 2023 by The American Society of Hematology2023 You do not currently have access to this content. Sign in via your Institution