Kdm3b, a histone lysine demethylase, belongs to the KDM3 (JMJD1) protein subfamily. It specifically removes dimethyl and monomethyl marks from lysine 9 on histone H3 and other non-histone proteins, thus regulating gene transcription. Dysregulation of Kdm3b is associated with various conditions, including infertility, obesity, metabolic syndromes, heart diseases, and cancers [3].

In fusion-positive rhabdomyosarcoma (FP-RMS), KDM3B inhibitors can disrupt the oncogenic activity of PAX3-FOXO1, suggesting a potential therapeutic approach for this pediatric sarcoma [1]. In IDH2-and TET2-mutant hematopoietic stem and progenitor cells (HSPCs), loss of Kdm3b reduces cell fitness, highlighting it as a genotype-specific vulnerability [2]. In invasive ductal carcinoma, the KDM3B-ETF1 fusion gene promotes metastasis by downregulating LMO2 via the WNT/β-catenin signaling pathway [4]. In acute promyelocytic leukemia (APL), knockdown of Kdm3B promotes cell-cycle progression, blocks granulocytic differentiation, and inhibits the ATRA-induced degradation of the PML/RARα oncoprotein [5]. In hepatocarcinoma HepG2 cells, ablation of Kdm3B by Nuclease technology retards the cell cycle and proliferation, and about 30% of knockout cells show mitotic spindle multipolarity [6].

In conclusion, Kdm3b plays crucial roles in multiple biological processes and disease conditions. Gene knockout and knockdown models have been instrumental in revealing its functions in cancers such as FP-RMS, invasive ductal carcinoma, APL, and hepatocarcinoma, as well as in hematopoietic disorders related to IDH2-and TET2-mutant HSPCs. These findings provide potential therapeutic targets for these diseases.