Sorafenib-related IL-15 production caused an increase in CD8<sup>+</sup>CD107a<sup>+</sup>IFN-γ<sup>+</sup> T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients.
Furthermore, IFN gene therapy strongly enhances anti-tumor activity of adoptively transferred T cells engineered with tumor-specific TCR or CAR, overcoming suppressive signals in the leukemia TME.
The identification of IFN regulatory factor 4 gene (IRF4) translocation in 8 out of 14 cases of cutaneous anaplastic large cell lymphomas (C-ALCLs) (Leukemia, 2009; 23(3):574-80) prompted us to study IRF4 locus status in different cutaneous T-cell lymphoma (CTCL) subtypes.
Leukemias with a -5/del(5q) have a higher expression of genes involved in cell cycle control (CCNA2, CCNE2, CDC2), checkpoints (BUB1), or growth (MYC), and loss of expression of the gene encoding IFN consensus sequence-binding protein (ICSBP).
To define the smallest region of overlap of deletions at chromosome band 9p21-22 and to clarify the involvement of p16, p15 and the IFN cluster gene in lymphoblastic leukemias, we used a multiplex polymerase chain reaction to construct a detailed map of deletions at 9p21-22.
These results demonstrate that fibroblast-mediated human IFN-alpha gene therapy is effective in treating leukemia and may achieve a better therapeutic effect when combined with Dox.
The distal breakpoints of the deletions (in relation to the centromere) in 14 glioma and leukemia cell lines have been mapped within the 400 kb IFN gene cluster located at band 9p21.