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 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 2 O 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 2 O 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.

Prognostic Value of CD44 Variant exon 6 Expression in Non-Small Cell Lung Cancer: a Meta-analysis

“…Fan et al performed a metaanalysis and demonstrated CD44v6 positive cells were significantly associated with poor overall survival in patients with colorectal cancer (OR=0.36, p=0.02) (Fan et al, 2012). Study by Chen suggested that CD44v6/v7 expression might be a prognostic indicator in patients with acute promyelocytic leukemia (Chen et al, 2012 consistent with longer survival in laryngeal squamous cell carcinoma patients. In lung cancer, the present studies showed CD44v6 may play an important role in lung carcinoma histogenesis and in determining the fate of neoplastic differentiation (Spaford et al, 1996).…”

CD44: a cancer stem cell marker and therapeutic target in leukemia treatment

“…For instance, individuals carrying the rs13347 TT and CT genotypes demonstrate higher CD44v expression level compared to those with the rs13347 CC genotype (57). The presence of various complex patterns of CD44 variant exons, particularly exon v6, has been observed in the majority of leukemia samples (58). The combination of CD44v6 and HA enhances cell resistance to apoptosis and activates the PI3K/Akt signaling pathway (42).…”

Acute Promyelocytic Leukemia: a Single Center Study from Southern Pakistan

“…There are a multiple unique features of this disease includes; potentially life-threatening coagulopathy, characteristic t(15;17) translocation, resulting in the PML-RARα΄ gene, unique sensitivity to all-trans-retinoic acid (ATRA), having potential for complete remission without chemotherapy and marrow aplasia and most curable (Bajpai et al, 2011;Chen et al, 2012;Imani-Saber and Ghafouri-Fard., 2014).…”