The DIS3L2 Knockout K-562 Polyclonal Cells represent a CRISPR/Cas9-engineered polyclonal knockout cell population in which the DIS3L2 gene has been disrupted, generating a heterogeneous loss-of-function model. This product is valuable for investigating the biological roles of DIS3L2 in a chronic myelogenous leukemia context, avoiding clonal bias inherent to single-cell-derived lines.
The host cell line K-562 is a suspension-adapted, lymphoblast-like cell line with hematopoietic progenitor characteristics, originally isolated from a female CML patient in blast crisis. These cells harbor the BCR-ABL1 fusion gene and the Philadelphia chromosome, driving constitutive tyrosine kinase activity and providing a robust model for leukemia biology, drug sensitivity testing, and inducible differentiation along erythroid and granulocytic lineages.
DIS3L2 encodes a 3′-5′ exoribonuclease that specifically processes uridylated RNA species. It is a critical effector in RNA surveillance, particularly in the LIN28A/B?CTUT4/TUT7?Clet-7 pathway. LIN28A/B proteins recruit terminal uridylyltransferases TUT4 (ZCCHC11) and TUT7 (ZCCHC6) to add 3′-oligo(U) tails to pre-let-7 microRNAs and certain mRNAs, marking them for DIS3L2-mediated degradation. Consequently, DIS3L2 knockout leads to aberrant accumulation of uridylated pre-let-7, impaired mature let-7 production, and derepression of oncogenic targets including HMGA2, KRAS, and c-MYC. DIS3L2 also regulates p53 mRNA stability and is linked to Perlman syndrome and Wilms tumor predisposition.
In the K-562 leukemia model, loss of DIS3L2 is expected to amplify proliferative and survival signals via let-7-dependent and independent mechanisms, potentially altering BCR-ABL1 downstream signaling and chemoresistance. This polyclonal knockout pool allows examination of DIS3L2??s role in RNA metabolism within Philadelphia chromosome-positive cells and provides a platform to screen for synthetic lethal interactions or drug sensitivities.
Researchers can employ this cell product in a spectrum of assays: quantitative RT-PCR for let-7 family members and target transcripts, RNA immunoprecipitation and RNA stability measurements, western blot analysis of pathway components, and functional assays including cell proliferation, apoptosis by flow cytometry, and colony formation. The cells are also suitable for in vivo xenograft tumor models to evaluate tumorigenicity and therapeutic responses. For further information, please contact Ascent Research.
