This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Grossbard ML, Press OW, Appelbaum FR, Bernstein ID, Nadler LM. Monoclonal antibody-based therapies of leukemia and lymphoma. Blood. 1992;80:863–78.
Walter RB, Appelbaum FR, Estey EH, Bernstein ID. Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood. 2012;119:6198–208.
Laszlo GS, Estey EH, Walter RB. The past and future of CD33 as therapeutic target in acute myeloid leukemia. Blood Rev. 2014;28:143–53.
Godwin CD, Gale RP, Walter RB. Gemtuzumab ozogamicin in acute myeloid leukemia. Leukemia. 2017;31:1855–68.
Walter RB. Investigational CD33-targeted therapeutics for acute myeloid leukemia. Exp Opin Investig Drugs. 2018;27:339–48.
Laszlo GS, Harrington KH, Gudgeon CJ, Beddoe ME, Fitzgibbon MP, Ries RE, et al. Expression and functional characterization of CD33 transcript variants in human acute myeloid leukemia. Oncotarget. 2016;7:43281–94.
Malik M, Simpson JF, Parikh I, Wilfred BR, Fardo DW, Nelson PT, et al. CD33 Alzheimer’s risk-altering polymorphism, CD33 expression, and exon 2 splicing. J Neurosci. 2013;33:13320–5.
Raj T, Ryan KJ, Replogle JM, Chibnik LB, Rosenkrantz L, Tang A, et al. CD33: increased inclusion of exon 2 implicates the Ig V-set domain in Alzheimer’s disease susceptibility. Hum Mol Genet. 2014;23:2729–36.
Lamba JK, Chauhan L, Shin M, Loken MR, Pollard JA, Wang YC, et al. CD33 splicing polymorphism determines gemtuzumab ozogamicin response in de novo acute myeloid leukemia: report from randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2017;35:2674–82.
Correnti CE, Laszlo GS, de van der Schueren WJ, Godwin CD, Bandaranayake A, Busch MA, et al. Simultaneous multiple interaction T-cell engaging (SMITE) bispecific antibodies overcome bispecific T-cell engager (BiTE) resistance via CD28 co-stimulation. Leukemia. 2018;32:1239–43.
Siddiqui SS, Springer SA, Verhagen A, Sundaramurthy V, Alisson-Silva F, Jiang W, et al. The Alzheimer’s disease-protective CD33 splice variant mediates adaptive loss of function via diversion to an intracellular pool. J Biol Chem. 2017;292:15312–20.
Humbert O, Laszlo GS, Sichel S, Ironside C, Haworth KG, Bates OM, et al. Engineering resistance to CD33-targeted immunotherapy in normal hematopoiesis by CRISPR/Cas9-deletion of CD33 exon 2. Leukemia. 2019;33:762–808.
Stewart RS, Drisaldi B, Harris DA. A transmembrane form of the prion protein contains an uncleaved signal peptide and is retained in the endoplasmic Reticulum. Mol Biol Cell. 2001;12:881–9.
Yamamoto K, Hayashishita M, Minami S, Suzuki K, Hagiwara T, Noguchi A, et al. Elimination of a signal sequence-uncleaved form of defective HLA protein through BAG6. Sci Rep. 2017;7:14545.
Acknowledgements
We thank Dr. Derek L. Stirewalt and Era Pogosova-Agadjanyan for provision of primary human AML specimens from the Fred Hutchinson Cancer Research Center/University of Washington Hematopoietic Diseases Repository. Research reported in this publication was supported by the Leukemia & Lymphoma Society (Translational Research Program, grant 6489–16) and the National Institutes of Health/National Cancer Institute (NIH/NCI) (R21-CA234203, P30-CA015704, and P50-CA100632 [MD Anderson Cancer Center Leukemia SPORE]). C.D.G. is supported by a fellowship training grant from the NIH/National Heart, Lung, and Blood Institute (NHLBI; T32-HL007093), an institutional K12 grant from the NIH/NCI (K12-CA076930) an American Society of Clinical Oncology/Conquer Cancer Foundation Young Investigator Award and an Alex’s Lemonade Stand Young Investigator Grant.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
HPK is a consultant to and has ownership interests with Rocket Pharma and Homology Medicines and is a consultant to CSL Behring and Magenta Therapeutics. RBW received laboratory research grants and/or clinical trial support from Agios, Amgen, Aptevo Therapeutics, Arog, BioLineRx, Jazz, Pfizer, Seattle Genetics, and Selvita; has ownership interests with Amphivena Therapeutics; and is (or has been) a consultant to Agios, Amphivena Therapeutics, Astellas, BiVictrix, Boehringer Ingelheim, Covagen, Emergent Biosolutions/Aptevo Therapeutics, Jazz, Kite, Pfizer, and Seattle Genetics. The other authors declare no competing financial interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Godwin, C.D., Laszlo, G.S., Wood, B.L. et al. The CD33 splice isoform lacking exon 2 as therapeutic target in human acute myeloid leukemia. Leukemia 34, 2479–2483 (2020). https://doi.org/10.1038/s41375-020-0755-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41375-020-0755-7
This article is cited by
-
The CD33 short isoform is a gain-of-function variant that enhances Aβ1–42 phagocytosis in microglia
Molecular Neurodegeneration (2021)
-
Targeting the membrane-proximal C2-set domain of CD33 for improved CD33-directed immunotherapy
Leukemia (2021)