Spalt-like transcription factor 4 isoform B (SALL4B) (SALL4B)

Spalt-like transcription factor 4 isoform B (SALL4B) is a truncated splice variant of the SALL4 oncofetal protein, characterized by the absence of central zinc-finger clusters (ZFC2 and ZFC3) found in the full-length SALL4A isoform [3, 18]. It serves as a master regulator of pluripotency and self-renewal in embryonic stem cells and is aberrantly re-expressed in approximately one-third of adult human cancers, including hepatocellular carcinoma and acute myeloid leukemia [1, 13]. SALL4B is increasingly recognized as a dominant oncogenic isoform that promotes cell survival, metastasis, and drug resistance by activating stemness pathways such as Wnt/beta-catenin and PI3K/AKT [11, 16]. While SALL4 is a major target for degradation by immunomodulatory drugs (IMiDs) like thalidomide—a mechanism that causes severe teratogenicity—recent studies suggest that SALL4B specifically may be resistant to IMiD-induced degradation, whereas SALL4A is susceptible [6, 8, 17]. This discovery has repositioned SALL4B as a high-priority target for next-generation non-IMiD molecular glues and peptide inhibitors designed to treat aggressive, SALL4-positive malignancies without the unintended developmental toxicities associated with broader SALL4 degradation [6, 20].

Other names

SALL4Sal-like protein 4Spalt-like transcription factor 4Zinc finger protein 607ZNF607DRRSHSAL4

Molecular glue-induced proteasomal degradation (via recruitment to the CRBN E3 ubiquitin ligase), competitive inhibition of protein-protein interactions (e.g., SALL4-RBBp4 interaction), and transcriptional repression or activation of target genes like PTEN and Bmi-1.