Proposed synergy of genetic alterations
| Genomic event . | Gene components . | Proposed synergy . |
|---|---|---|
| Unbalanced CIITA rearrangement | SOCS1, CIITA, CIITA fusion partners (eg, PDL1 and PDL2) | Impaired CIITA function, overexpression of fusion partners, and deletion of tumor suppressor genes might be simultaneous consequences of a single unbalanced translocation event: (1) proliferative advantage through increased JAK-STAT signaling in the malignant cells by deletion of SOCS1 cooperates with escape from immune surveillance by (2) overexpression of PD-1 ligands and (3) down-regulation of HLA class II |
| Chromosomal gain of 9p | JAK2, JMJD2C, PDL1, PDL2 | Overexpression of JAK2, JMJD2C, PDL1, and PDL2 is linked as these genes are part of the same amplicon involving cytoband 9p24.1: (1) JAK2 overexpression increases JAK-STAT signaling promoting proliferation; (2) JAK2 transcriptionally augments PD-1 ligand expression inhibiting T-cell activation in the tumor microenvironment and (3) cooperates with JMJD2C to alter the epigenome in PMBCL by histone H3 modifications promoting proliferation and survival |
| Genomic event . | Gene components . | Proposed synergy . |
|---|---|---|
| Unbalanced CIITA rearrangement | SOCS1, CIITA, CIITA fusion partners (eg, PDL1 and PDL2) | Impaired CIITA function, overexpression of fusion partners, and deletion of tumor suppressor genes might be simultaneous consequences of a single unbalanced translocation event: (1) proliferative advantage through increased JAK-STAT signaling in the malignant cells by deletion of SOCS1 cooperates with escape from immune surveillance by (2) overexpression of PD-1 ligands and (3) down-regulation of HLA class II |
| Chromosomal gain of 9p | JAK2, JMJD2C, PDL1, PDL2 | Overexpression of JAK2, JMJD2C, PDL1, and PDL2 is linked as these genes are part of the same amplicon involving cytoband 9p24.1: (1) JAK2 overexpression increases JAK-STAT signaling promoting proliferation; (2) JAK2 transcriptionally augments PD-1 ligand expression inhibiting T-cell activation in the tumor microenvironment and (3) cooperates with JMJD2C to alter the epigenome in PMBCL by histone H3 modifications promoting proliferation and survival |