A novel CD44 antibody identifies an epitope that is aberrantly expressed on acute lymphoblastic leukaemia cells.
Previous studies have shown that the antibody 7H9D6 identifies CD44, a glycoprotein receptor for hyaluronic acid. 7H9D6 recognizes an epitope of CD44 that is not always present on CD44 molecules. The 7H9D6 antibody bound to the hyaluronic acid binding domain of CD44 and inhibited cell adhesion to immobilized hyaluronic acid. However, the expression of the 7H9D6 epitope was not sufficient for hyaluronic acid binding. Immunofluorescent staining with 7H9D6 revealed a punctate surface staining pattern, suggesting that CD44 molecules recognized by 7H9D6 are located in clusters on the cell surface. In contrast, other CD44 antibodies produced a uniform staining pattern. Early bone marrow B cells were negative for 7H9D6 but reactive with other CD44 monoclonal antibodies. In contrast, leukaemic cells from 65% of patients (28 of 43) with B lineage acute lymphoblastic leukaemia bound 7H9D6. Patients expressing the 7H9D6 epitope on their leukaemic cells had an increased risk of death (HR 3.5 95% CI 1.1-10.9, P = 0.029) and of disease relapse (HR 3.2 95% CI 1.2-8.5, P = 0.017) when corrected for white cell count. This antibody may be useful for the detection of residual disease in B lineage acute lymphoblastic leukaemia and as a prognostic indicator and for the study of CD44 function.
Bendall
Linda J
LJ
Westmead Institute for Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia. linda_bendall@wmi.usyd.edu.au
James
Alexander
A
Zannettino
Andrew
A
Simmons
Paul J
PJ
Gottlieb
David J
DJ
Bradstock
Kenneth F
KF
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D002448:Cell Adhesion; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology* / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D007231:Infant, Newborn; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000939:Epitopes; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid