Altered patterns of CD44 epitope expression in human chronic and acute myeloid leukemia.
Abnormal expression of different isoforms of CD44 has been found to characterize many types of malignant cells although data for human acute and chronic myeloid leukemia is limited. In this study, we have identified significant, albeit variable, increases in these diseases of the frequency of both light density and CD34+ cells expressing two particular CD44 epitopes, neither of which is commonly found on normal human marrow cells. One of these epitopes is unique to exon v10-containing isoforms of CD44. The other is located in the common region of CD44 and was previously revealed on T cells only after their activation. Interestingly, another T cell activation-associated epitope was found to be expressed on a high proportion of normal marrow cells including the CD34+ subset and this remained the case for most of the primary leukemic samples evaluated. As expected, >90% of cells in all primary normal and leukemic samples expressed high levels of CD44, as shown by their reactivity with an antibody specific for the CD44 hyaluronan-binding site. To begin investigating how expression of the CD44 epitopes seen more commonly on leukemic than on normal CD34+ cells may be modulated, and to identify potentially associated effects on the hyaluronan-binding ability of the CD44 expressed, the effect of phorbol ester treatment on these properties of CD44 were examined. For these studies, a panel of five different human leukemic cell lines that were found to exhibit different patterns of CD44 expression and function in the absence of phorbol ester were used. Both the level and the hyaluronan-binding properties of CD44 could be stimulated in some, but not all, of these leukemic cell lines. Taken together, our findings indicate that CD44 expression is perturbed in a variety of leukemic populations suggesting a possible relationship to some of the pathogenetic features they share.
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
S
S
Ghaffari
G J
GJ
Dougherty
A C
AC
Eaves
C J
CJ
Eaves
D014408:Biomarkers, Tumor; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000276:immunology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*
D014408:Biomarkers, Tumor; D000939:Epitopes; D018960:Hyaluronan Receptors