MGSSHHHHHH SSGLVPRGSH MGSMGNSLLR ENRRQQNTQE MPWNVRMQSP KQRTSRCWDH HIAEGCFCLP WKKILIFEKR QDSQNENERM SSTPIQDNVD QTYSEELCYT LINHRVLCTR PSGNSAEEYY ENVPCKAERP RESLGGTETE YSLLHMPSTD PRHARSPEDE YELLMPHRIS SHFLQQPRPL MAPSETQFSH L.
Germinal Center-Associated, Signaling and Motility (GCSAM), also known as Human Germinal Center-Associated Lymphoma (HGAL), is a protein specifically expressed in germinal center lymphocytes. This protein plays a crucial role in regulating B-cell receptor signaling and cell motility, which are essential processes in the immune response and lymphomagenesis .
GCSAM contains several important domains, including a putative PDZ-interacting domain, an immunoreceptor tyrosine-based activation motif (ITAM), and two putative SH2 binding sites . These domains suggest that GCSAM is involved in signal transduction pathways, which are critical for the regulation of cellular activities.
High expression of HGAL is associated with prolonged survival in patients with diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL) . HGAL inhibits lymphoma dissemination by interacting with multiple cytoskeletal proteins, thereby affecting cell motility through various mechanisms . Specifically, HGAL interacts with tubulin, which contributes to its effects on cell motility .
The cytoskeleton, functioning as a dynamic regulator of cellular shape and membrane organization in lymphocytes, plays a key role in B-cell motility and B-cell receptor (BCR) signaling . Tight regulation of the cytoskeleton is critical for intact and effective immunity. Alterations in cytoskeleton function may contribute to lymphoma pathogenesis . HGAL regulates B-cell receptor signaling and cell motility by interacting with cytoskeletal proteins, thereby influencing lymphoma motility and spread .
HGAL is a reliable marker for diagnosing diffuse large B-cell lymphoma, particularly in cases where CD10 is negative . It is also useful in diagnosing T follicular helper (TFH) cell-derived lymphomas, including angioimmunoblastic T-cell lymphoma . The expression of HGAL is associated with early-stage DLBCL, potentially limiting lymphoma dissemination and improving patient survival .