Abstract
Pin1 is a peptidyl-prolyl-isomerase catalysing conformational changes on ser/thr-pro-sites of proteins, and has been shown to play a pivotal role for the activity of cell cycle regulating proteins in breast and prostate cancer cells. Overexpression of Pin1 has been found in many cancers, and we here present first data on its expression in blast cells of patients with acute myeloid leukaemia (AML). Having documented Pin1 expression in leukemic cell lines with highest expression levels in the promyelocytic leukemia cell line HL60, we analyzed the expression of Pin1 in bone marrow samples with high blast counts from 24 pediatric and 28 adult patients with AML by semiquantitative RT-PCR and flow cytometry. Expression levels varied considerably, ranging from undetectable in 16 of 52 cases, to very high levels of up to 13.7 units normalized on abl-expression in the RT-PCR. Pin1 levels did not correlate with patient age, nor the expression of progenitor or myeloid differentiation markers on the blast cell population. Also, Pin1 level did not segregate with FAB classification, nor the prognostic implications of cytogenetic findings. Comparing Pin1-negative to Pin1-positive leukaemia cases at a median observation time of 32 months by Kaplan-Meier analysis, we found a tendency towards better event free (p=0.01) and overall survival (p=0.058) for the Pin1-positive cases. In summary, Pin1 was found in the leukemic blast cells of most patients with AML, and further investigations on prognostic significance and function of Pin1 in AML appear warranted.
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