CRISPR/Cas9 gene editing clarifies the role of CD33 SNP rs12459419 in gemtuzumab ozogamicin-mediated cytotoxicity

The single-nucleotide polymorphism (SNP) rs12459419 is located at the intron/exon junction of CD33 exon2. When exon2 is skipped by this CD33 SNP, the full-length CD33 (CD33FL) is converted to a short CD33 isoform (CD33D2). Since gemtuzumab ozogamicin (GO) only recognizes CD33FL, the CD33 SNP may aff...

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Bibliographic Details
Published in:International journal of hematology 2024-08, Vol.120 (2), p.194-202
Main Authors: Oya, Shuki, Ozawa, Hidetoshi, Nakamura, Takayuki, Mori, Akira, Ochi, Sorahiko, Maehiro, Yoshimi, Umeda, Masahiro, Takaki, Yusuke, Fukuyama, Toshinobu, Yamasaki, Yoshitaka, Yamaguchi, Maki, Aoyama, Kazutoshi, Mouri, Fumihiko, Nagafuji, Koji
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Cell lines
Cloning
CRISPR
CRISPR-Cas Systems
Cytotoxicity
Editing
Gemtuzumab
Gemtuzumab ozogamicin
Gene Editing - methods
Gene expression
Genetic modification
Genome editing
Hematology
Humans
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - genetics
Medicine
Medicine & Public Health
Nucleotides
Oncology
Original Article
Polymorphism
Polymorphism, Single Nucleotide
Proteins
Sialic Acid Binding Ig-like Lectin 3 - genetics
Single-nucleotide polymorphism
Toxicity
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Description
Summary:The single-nucleotide polymorphism (SNP) rs12459419 is located at the intron/exon junction of CD33 exon2. When exon2 is skipped by this CD33 SNP, the full-length CD33 (CD33FL) is converted to a short CD33 isoform (CD33D2). Since gemtuzumab ozogamicin (GO) only recognizes CD33FL, the CD33 SNP may affect the clinical efficacy of GO. To elucidate the significance of CD33 SNP on GO reactivity, we leveraged the CRISPR/Cas9 genome-editing system to create OCI-AML3 cell lines with specifically modified CD33 SNPs. Levels of CD33 D2 mRNA were significantly higher in the T/T clone ( p  
ISSN:0925-5710
1865-3774
1865-3774
DOI:10.1007/s12185-024-03803-2