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Prognostic Significance of CD44v6/v7 in Acute Promyelocytic Leukemia

  • Chen, Ping (Fujian Institute of Hematology, Affiliated Union Hospital of Fujian Medical University, Fujian Provincial Key Laboratory on Hematology) ;
  • Huang, Hui-Fang (Fujian Institute of Hematology, Affiliated Union Hospital of Fujian Medical University, Fujian Provincial Key Laboratory on Hematology) ;
  • Lu, Rong (Fujian Institute of Hematology, Affiliated Union Hospital of Fujian Medical University, Fujian Provincial Key Laboratory on Hematology) ;
  • Wu, Yong (Fujian Institute of Hematology, Affiliated Union Hospital of Fujian Medical University, Fujian Provincial Key Laboratory on Hematology) ;
  • Chen, Yuan-Zhong (Fujian Institute of Hematology, Affiliated Union Hospital of Fujian Medical University, Fujian Provincial Key Laboratory on Hematology)
  • Published : 2012.08.31

Abstract

CD44v, especially splice variants containing exon v6, has been shown to be related closely to development of different tumors. High levels of CD44v6/v7 have been reported to be associated with invasiveness and metastasis of many malignancies. The objective of this study was to detect expression of CD44v6-containing variants in patients 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, ligation into T vectors and positive clone sequencing were used to detect CD44 v6-containing variant isoforms in 23 APL patients. Real-time quantitative PCR of the CD44v6/v7 gene was performed in patients with APL and in NB4 cells that were treated with all-trans retinoic acid (ATRA) or arsenic trioxide ($As_2O_3$). Sequencing results identified four isoforms (CD44v6/v7, CD44v6/v8/v10, CD44v6/v8/v9/v10, and CD44v6/v7/v8/v9/v10) in bone marrow mononuclear cells of 23 patients with APL. The level of CD44v6/v7 in high-risk cases was significantly higher than those with low-risk. Higher levels of CD44v6/v7 were found in three patients with central nervous system relapse than in other patients inthe same risk group. Furthermore, in contrast to ATRA, only $As_2O_3$ could significantly down-regulate CD44v6/v7 expression in NB4 cells. Our data suggest that CD44v6/v7 expression may be a prognostic indicator for APL.

Keywords

CD44v;acute promyelocytic leukemia;extramedullary relapse;prognosis;$As_2O_3$

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