Clec12a is required for the pathogenesis of NUP98::NSD1 AML Journal Article
| Authors: | Mohanty, S.; Cano, F. C.; Gabdoulline, R.; Lai, C. K.; Othman, B.; Sudarsanam, H.; Eder, T.; Grebien, F.; Lipka, D. B.; Henschler, R. |
| Article Title: | Clec12a is required for the pathogenesis of NUP98::NSD1 AML |
| Abstract: | NUP98::NSD1 is one of the most recurring nucleoporin 98 (NUP98) fusions in acute myeloid leukemia (AML). NUP98::NSD1 positive AML is often associated with adverse outcomes and poor response to conventional treatments. However, limited studies have been done to identify new potential targets to develop better treatment approaches. The C-type lectin domain family 12 member A (CLEC12A) is a cell surface receptor that is differentially expressed in leukemic stem cells compared with healthy hematopoietic stem cells. We found a strong CLEC12A overexpression in both NUP98::NSD1 patients and murine AML cells transformed with the NUP98::NSD1 fusion oncogene. To understand the role of Clec12a in NUP98::NSD1 AML, we depleted Clec12a expression in NUP98::NSD1+NRASG12Dimmortalized cells using the CRISPR/Cas9 approach. NUP98::NSD1+NRASG12D/Clec12a knockout cells had higher apoptosis levels and lower colony numbers in vitro compared with NUP98::NSD1+NRASG12D/Clec12a wild-type cells. Importantly, the deletion of Clec12a significantly reduced leukemic engraftment and prolonged survival of the NUP98::NSD1+NRASG12D murine model. Our data suggest to further explore CLEC12A as a potential target for the treatment of NUP98::NSD1 AML. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | controlled study; protein expression; unclassified drug; gene mutation; pathogenesis; fluorouracil; nonhuman; flow cytometry; dna synthesis; mouse; animal tissue; cell cycle; reverse transcription polymerase chain reaction; apoptosis; gene expression; animal experiment; animal model; adverse outcome; interleukin 6; immunophenotyping; hematopoietic stem cell; receptor; rna extraction; nucleoporin 98; acute myeloid leukemia; high throughput sequencing; sanger sequencing; female; article; rna sequencing; crispr cas system; adobe illustrator cs5.1; axiocamera 5s microscope; bd lsrii flow cytometer; beckman coulter cytoflex s analyzer; flowjo software version 10.0.7; graphpad prism version 7 software; novaseq 6000 instrument; olympus ckx31; rneasy kit; stepone plus cycler; c type lectin domain family 12 member a |
| Journal Title: | Blood Advances |
| Volume: | 9 |
| Issue: | 15 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2025-08-12 |
| Start Page: | 3887 |
| End Page: | 3899 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2024015739 |
| PUBMED: | 40334081 |
| PROVIDER: | scopus |
| PMCID: | PMC12332935 |
| DOI/URL: | |
| Notes: | Source: Scopus |
