Prognostic Significance of CD44v6/v7 in Acute Promyelocytic Leukemia

Abstract

CD44v, especially splice variants containing exon v6, has been shown to be related closely to development ofdifferent tumors. High levels of CD44v6/v7 have been reported to be associated with invasiveness and metastasisof many malignancies. The objective of this study was to detect expression of CD44v6-containing variants inpatients with acute promyelocytic leukemia (APL) and evaluate the potential of CD44v6/v7 for risk stratification.Reverse transcription polymerase chain reaction (RT-PCR) followed by PCR product purification, ligationinto T vectors and positive clone sequencing were used to detect CD44 v6-containing variant isoforms in 23APL patients. Real-time quantitative PCR of the CD44v6/v7 gene was performed in patients with APL and inNB4 cells that were treated with all-trans retinoic acid (ATRA) or arsenic trioxide (As2O3). Sequencing resultsidentified four isoforms (CD44v6/v7, CD44v6/v8/v10, CD44v6/v8/v9/v10, and CD44v6/v7/v8/v9/v10) in bonemarrow mononuclear cells of 23 patients with APL. The level of CD44v6/v7 in high-risk cases was significantlyhigher than those with low-risk. Higher levels of CD44v6/v7 were found in three patients with central nervoussystem relapse than in other patients inthe same risk group. Furthermore, in contrast to ATRA, only As2O3 couldsignificantly down-regulate CD44v6/v7 expression in NB4 cells. Our data suggest that CD44v6/v7 expressionmay be a prognostic indicator for APL.