Expression of CD44 variant exons in acute myeloid leukemia is more common and more complex than that observed in normal blood, bone marrow or CD34(+)cells

CD44 is an adhesion molecule that is expressed on hematopoietic cells and h as been implicated in the interactions between bone marrow stromal layers a nd hematopoietic progenitors. The expression of variant forms of CD44, part icularly forms containing exon v6, have been associated with poor prognosis in a number of hematological malignancies. The expression of CD44 variants on normal bone marrow (BM), peripheral blood (PBMC) and CD34(+) hematopoie tic progenitors was compared with those expressed on blasts from 30 patient s with acute myeloid leukemia (AML). Normal BM, PBMC and CD34(+) progenitor cells were negative for all variants tested by flow cytometry. In contrast exon v3 was expressed on 13%, v4 on 67%, v5 on 19%, v6 on 7% and v7 on 65% of AML cases. RT-PCR and Southern blotting revealed the expression of exon s v3, v6, v8, v9 and v10 in normal bone marrow and peripheral blood mononuc lear cells and the expression of exons v3, v6, v8 and v10 in CD34(+) progen itors. A more complex pattern of variant exon expression was observed in le ukemic samples in comparison to normal hematopoietic cells. Sixty-two perce nt of AML cases expressed exon v3 and 70% exon v6. Exons v4 and v5 were not detected while exons v7, v8, v9 and v10 were detected in 21, 83, 71 and 92 % of cases, respectively. In summary, our data demonstrate a striking incre ase in the complexity of CD44 variant expression in cells from patients wit h AML, along with surface expression of some variant CD44 proteins. Further analysis will be directed at how these alter the interaction of leukemic b lasts with the bone marrow microenvironment and their diagnostic, prognosti c and therapeutic potential.