title: Recombinant human CD19-ligand protein as a potent anti-leukaemic agent.
abstract: We report the cloning and characterization of a novel 54-kDa high-mobility group (HMG)-box protein as the ligand for the human pan-B cell co-receptor CD19 (CD19-L), which interacts with the extracellular domain of CD19 in trans. CD19-L is the first CD19-specific recombinant human protein with potent anti-leukaemic activity against B-lineage acute lymphoblastic leukaemia (ALL), the most common form of childhood cancer and the second most common form of acute leukaemia in adults. Soluble recombinant CD19-L protein exhibited exquisite specificity for the extracellular domain of CD19 and strong binding to the surface of B-lineage leukaemia/lymphoma cells. Engagement of CD19 co-receptor on B-lineage ALL cells with CD19-L perturbed the CD19-associated signalling 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. The identification of human CD19-L may lead to therapeutic innovation for B-lineage ALL and other B-lineage lymphoid malignancies as well as B-cell lymphoproliferative states and systemic autoimmunity.
authors.affiliation: Institute for Pediatric Clinical Research, Children's Hospital, LA, CA, USA. fmuckun@chla.usc.edu
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Sanjive
authors.initials: S
authors.lastname: Qazi
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Zahide
authors.initials: Z
authors.lastname: Ozer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003001:Cloning, Molecular; D020869:Gene Expression Profiling / Q000379:methods; D024002:HMGB Proteins / Q000235:genetics; D006801:Humans; D008024:Ligands; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured
chemical_list: D018941:Antigens, CD19; D000970:Antineoplastic Agents; D024002:HMGB Proteins; D008024:Ligands; D011993:Recombinant Fusion Proteins