Significance of Notch Expression in Acute Myeloid Leukemia

Abstract

BACKGROUND: Notch is a gene family encoding receptors to transduce intercellular signals involved in cell-fate determination. Although several lines of evidence indicate that abnormal Notch signaling may contribute to neoplastic transformation, little is known regarding the role of Notch in the pathogenesis of leukemia. METHODS: To explore the functional significance of Notch1 in acute myeloid leukemia (AML), the expression of Notch1 and its association with survivin and p27Kip1 expression was examined in 50 patients with de novo AML. RESULTS: Notch1 transcripts were expressed in 40 (80%) cases with a variable degree of expression, and the fraction of AML cells in the G0/G1 phase was higher in Notch1-positive cases than in Notch1-negative cases. Survivin was shown to be present in 38 (76.0%) cases, and Notch1 expression highly correlated with survivin mRNA expression (r=0.7170, P<0.001). p27Kip1 was present in 40 (80.0%) cases of AML and p27Kip1 expression was significantly associated with Notch1 expression (r=0.8770, P<0.001). Except for one case, the simultaneous expression of survivin and p27Kip1 was not seen in all cases that were negative for Notch1 expression. There were no differences in clinical outcomes according to Notch1 expression. CONCLUSION: Notch1 expression was a frequent event and has functional significance in the alteration of the cell cycle in AML cells. Notch1 expression was also significantly associated with survivin and p27kip1 expression in AML cells. To evaluate the clinical significanceand functional role of Notch1 expression in the aberrant regulation of survivin and p27Kip1 expression in de novo AML, a further study with a larger number of patients is necessary.