Cancer name Acute Lymphoid Leukemia
Cancer Type ALL
Immunotherapy type Adoptive Cell Therapy
Treatment CART-19
Drugstatus Approved, Investigational
Drugbank ID DB13881
Checkpoints NA
Signature Type Protein
Signature SRSF3
Official Symbol SRSF3
Mode of action PROT_NR_DOWN
Description for ‘mode of action’:the ‘mode of action’ for signature is composed of three parts: A_B_C. A describes the level at which the corresponding signature changes, it may contain the following values: TRAN(translation), PROT(protein), CE(cell), METH(methylation), AC(acetylation), PHOS(phosphorylation), MU(mutation), SNP(single nucleotide polymorphism), GLYC(glycosylation) and PATH(pathway). B describes the corresponding signature in which cancer immunotherapy condition group has changed, it may contain the following values: R (immunotherapy response group), NR(immunotherapy non-response group), D (Immunotherapy group), ND (No immunotherapy group). C describes the change detail (specific direction) of the corresponding signature, it may contain the following values: UP (High gene/protein expression or increased cellular abundance or enhanced epigenetic modification), DN (Low gene/protein expression or reduced cellular abundance or attenuated epigenetic modifications), LOSS (deletion mutation), GAIN (gain mutation),Other. For example, the search/browse detail result for CD274 was “PROT_R_UP”, it can be interpreted that the protein level of CD274 was upregulated in immunotherapy response individuals.
Experimental clinical trail
Description In both cases, relapsed leukemias expressed lower amounts of SRSF3. Also, two other post–CART-19 relapses, CHOP107R and CHOP133R (for which matched baseline samples were not available), expressed even lower levels of this protein. In parallel, we meas-ured the protein levels of hnRNPC1/C2 and hnRNPA1, but there was no consistent pattern of change for either of these splicing factors in paired post– versus pre–CART-19 samples. Taken together, these results suggest that SRSF3 insufficiency in relapsed leukemias could be at least partly responsible for the abundance of the CD19 Δex2 isoform.
PMID 26516065
Title Convergence of Acquired Mutations and Alternative Splicing of<U+00A0>CD19<U+00A0>Enables Resistance to CART-19 Immunotherapy