Cyclic nucleotide phosphodiesterase 7B mRNA: an unfavorable characteristic in chronic lymphocytic leukemia.

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Cyclic nucleotide phosphodiesterase 7B mRNA: an unfavorable characteristic in

chronic lymphocytic leukemia.

L Zhang, F Murray, LZ Rassenti, M Pu, C , JR Kanter, A Greaves, K Messer,

TJ Kipps, and PA Insel

Int J Cancer, November 30, 2010;

Departments of Pharmacology, University of California, San Diego, La Jolla, CA

92093.

A cost- and time-efficient means to define the prognosis of patients with

chronic lymphocytic leukemia (CLL) is desirable but does not yet exist. Based on

evidence that CLL cells have enhanced expression of the cyclic nucleotide

phosphodiesterase isoform 7B (PDE7B), we hypothesized that PDE7B expression

might provide such information. We assessed PDE7B mRNA expression using

quantitative real-time PCR (QPCR) in peripheral blood mononuclear cells isolated

from 85 patients and 30 normal subjects. We compared PDE7B mRNA expression with

that of other disease features to determine if its expression correlates with

the prognosis of patients with CLL. We found that CLL patients with PDE7B mRNA

levels in the top quartile (>9-fold elevation relative to normal controls) have

a several-year shorter median time-to-treatment (TTT, 36 months) compared to

that of patients whose CLL cells express lower levels of PDE7B mRNA (TTT, 77

months, P=0.001). High PDE7B mRNA expression correlates with expression of

Zeta-chain-associated protein kinase 70 (ZAP-70), unmutated immunoglobulin heavy

chain variable (IGHV) region genes and ?2 microglobulin (?2M), but use of a

multivariate model revealed that high PDE7B mRNA expression independently

predicts a short TTT, even after adjusting for several other disease

characteristics (ZAP-70 or CD38 expression, IGHV mutation status, Rai status).

High expression of PDE7B is an unfavorable characteristic in CLL. Assessment of

PDE7B mRNA expression thus appears to be a clinically useful biomarker to define

the prognosis of patients with CLL.

PMID: 21120911