A STRONG EXPRESSION OF CD44-6V CORRELATES WITH SHORTER SURVIVAL OF PATIENTS WITH ACUTE MYELOID-LEUKEMIA

CD44 is a ubiquitous cell-surface glycoprotein that displays many vari ant isoforms (CD44v) generated by alternative splicing of exons 2v to 10v. The expression of variant isoforms is highly restricted and corre lated with specific processes, such as leukocyte activation and malign ant transformation. We have herein studied CD44v expression in acute m yeloid leukemia (AML) and, for comparison, in normal myelopoiesis. Pro tein expression of total CD44 and of CD44-3v, -6v, and -9v isoforms ha s been measured using specific monoclonal antibodies and flow cytometr y, The composition of variant exon transcripts has been analyzed by se mi-quantitative reverse transcriptase-polymerase chain reaction follow ed by Southern hybridization with exon-specific probes. Our data show that (1) CD44-6v isoforms are expressed on 12.0% +/- 2.5% of normal CD 34(+) cells; this expression is sharply upregulated through monopoiesi s and, inversely, downregulated during granulopoiesis. Also, CD44-3v a nd CD44-9v isoforms are detected on 10% and 14% of normal monocytes, r espectively. (2) Sixty-nine from a total of 95 AML patients display a variable proportion (range, 5% to 80%) of CD44-6v(+) leukemic cells. ( 3) A shorter overall survival characterizes the group of AML patients displaying more than 20% of CD44-6v(+) leukemic cells (8 months v 18 m onths, P<.02). These data suggest, for the first time, that the protei n expression of CD44-6v containing isoforms may serve as a new prognos tic factor in AML. (C) 1998 by The American Society of Hematology.