Recombinant Protein Ligand Triggers Apoptosis in Leukemia Cells

Cancer researchers have bioengineered a protein ligand that binds to a protein on the surface of B-lineage leukemia/lymphoma cells and induces the cancer cells to enter an apoptotic mode.

The cancer cell-surface protein is known as CD19. This protein appears on cells comprising B-lineage acute lymphoblastic leukemia (ALL), the most common cancer occurring in children and adolescents. Another protein, CD19-L (CD19-ligand), is expressed on the surface of T-lymphocytes and it allows them to bind selectively to the CD19 receptor on the surface of B-lineage leukemia cells and on leukemic stem cells that are responsible for the survival and expansion of the leukemia cell population. Binding of CD19-L to leukemia cells triggers molecular pathways leading to cell death.

Investigators at the University of Southern California (Los Angeles, USA) reported in the February 17, 2011, online edition of the British Journal of Haematology that they had created a soluble recombinant form of CD19-L protein that exhibited specificity for the extracellular domain of CD19 and strong binding to the surface of B-lineage leukemia/lymphoma cells.

The association of CD19 coreceptor on B-lineage ALL cells with the recombinant CD19-L perturbed the CD19-dependent signaling network, altering the expression levels of multiple genes directly involved in regulation of apoptosis, and triggered rapid apoptotic cell death in a CD19-specific manner. CD19-L killed even those leukemia cells that were highly resistant to both standard chemotherapy drugs and radiation.

"We need new antileukemia therapies capable of killing chemotherapy-resistant leukemia cells in patients with relapsed ALL. These are the cells that are the most difficult to treat. The challenge is to kill these cells while leaving healthy cells intact,” said first author Dr. Fatih Uckun, professor of pediatrics at the University of Southern California.

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