Protein possible anti-leukaemia agent

A protein, CD19-ligand, demonstrates a promising cure for one of the most common forms of childhood cancer: Acute Lymphoblastic Leukaemia (ALL).

The ALL cells are recognized as mutagens, which leads to an immune response and the generation of antibodies against the cancer. Researchers Fatih M. Uckun and Hong Ma, alongside others, began working with a series of basic procedures which finally led to the cloning of part of the DNA which directly codes for part of the CD19 receptor. This part of DNA was then compared with the predetermined gene sequences within the GeneBank Database. The resulting DNA sequence was further developed to form a specific secondary structure.

The researchers discovered that CD19 receptor molecules regulate B-lymphocytes released during an immune response against the primary leukaemia cells. By interacting with its co-receptor molecules, CD19 allows the smooth ‘development, proliferation, activation and differentiation’ of B-lymphocytes. However, the interaction between CD19-ligands and leukaemia results in cell death which assists in the regulation of immune responses and the prevention of autoimmunity. In CD19+ leukaemia cells this interaction results in an altered set of signals being sent which cause cell death. Hence, the structure and bonding of the ligand with its co-receptor determines the fate of the cell.

CD19-L was then tested as a down-regulator of leukaemic activity in ALL cells with CD19 positive co-receptors. At this stage the interaction between CD19 co-receptors and CD19-L altered the regulation of genes; the down-regulated genes were analysed in greater detail, and lead the researchers to the conclusion that CD19-L had a significant effect on cell signalling, causing cell death and gene expression. The experiment is furthered by the treatment of chemotherapy resistant ALL CD19 positive cells with CD19-L concluding that CD19-L also causes cell death in relapsed ALL cells (CD19+).

The importance of determining CD19-L binding and functionality lies in the recovery of patients with relapsed ALL. As lead researcher Fatih Uckun says “These are the cells that are the most difficult to treat. The challenge is to kill these cells while leaving healthy cells intact.” The major advantage of CD19 is its specific and ample expression on leukaemic cells. CD19-Ligands are potential agents for the transport of cytotoxic materials to leukaemic cells, and may be a more effective and less damaging solution to an on-going problem.