PMLBCL : JAK-STAT Signaling Cascade

Comments:
JAK-STAT Signaling Cascade: This is another major pathway regulating cell proliferation that is altered in primary mediastinal large B-cell lymphomas (PMLBCL). It is activated by interleukin (IL) receptors, mainly IL-4 and IL-13. Amplification of 9p24.1 region on chromosome 9 (containing genes encoding JAK2, PDL1 & PDL2) has been found in approximately 63% of PMLBCL cases. This correlates with JAK2 overexpression and JAK-STAT cascade activation. It results in constitutive expression of several key genes required to initiate and/or maintain malignant transformation.

Overexpression of PDL1 and PDL2 leads to an exhaustion of T-cells and helps tumor cells escape from immunosurveillance. Whole transcriptome studies have shown alterations in several negative regulators of JAK-STAT pathway, such as SOCS1 and PTPN1. Another mechanism is upregulation of STAT6 due to an activating point mutation (36% of PMLBCL cases). These alterations cause JAK-STAT cascade activation and cell proliferation.

Image source: Bose, S. et al. Targeting the JAK/STAT Signaling Pathway Using Phytocompounds for Cancer Prevention and Therapy. Cells 2020, 9, 1451. Used under: Creative Commons Attribution License.