Evidence map›Paper›PMID 38853211›Full record

ArticleInternational journal of hematology2024

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

Shuki Oya, Hidetoshi Ozawa, Takayuki Nakamura, Akira Mori, Sorahiko Ochi, Yoshimi Maehiro, Masahiro Umeda, Yusuke Takaki, Toshinobu Fukuyama, Yoshitaka Yamasaki and 4 more

Abstract read
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Article in International journal of hematology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Shuki OyaDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Hidetoshi OzawaDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Takayuki NakamuraDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Akira MoriDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Sorahiko OchiDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Yoshimi MaehiroDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Masahiro UmedaDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Yusuke TakakiDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Toshinobu FukuyamaDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Yoshitaka YamasakiDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Maki YamaguchiDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Kazutoshi AoyamaDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Fumihiko MouriDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Koji NagafujiDivision of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. knagafuji@med.kurume-u.ac.jp.ORCID http://orcid.org/0000-0003-4795-121X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 < 0.001), but CD33D2 protein was not detectable in any clones. There was no significant difference in CD33FL mRNA expression across edited clones, and CD33FL protein expression was lowest in T/T clones, followed by T/C and C/C. Cytotoxicity assays revealed that the IC50 of GO was significantly lower in T/C and C/C clones than in the T/T clone (p < 0.001). Our study demonstrated a difference in GO-induced cytotoxicity in CD33 SNP-edited clones, clearly indicating that at least one CD33 SNP allele, rs12459419 C, is important for sensitivity to GO.

Indexed as

CRISPR-Cas SystemsGemtuzumabGene EditingPolymorphism, Single NucleotideSialic Acid Binding Ig-like Lectin 3Cell Line, TumorHumansLeukemia, Myeloid, AcuteCD33 protein, humanGemtuzumabSialic Acid Binding Ig-like Lectin 3CD33CRISPR/Cas9 gene editingGemtuzumab ozogamicinSingle-nucleotide polymorphisms

Identifiers

PMID38853211

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.