Cyclic nucleotide phosphodiesterase 7B mRNA: an unfavorable characteristic in chronic lymphocytic leukemia.
A cost- and time-efficient means to define the prognosis of patients with chronic lymphocytic leukemia (CLL) is desirable but does not yet exist. On the basis of the 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 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 (greater than ninefold 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 β2 microglobulin (β2M), but use of a multivariate Cox 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 and 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.
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0636, USA.
Lingzhi
L
Zhang
Fiona
F
Murray
Laura Z
LZ
Rassenti
Minya
M
Pu
Colleen
C
Kelly
Joan R
JR
Kanter
Andrew
A
Greaves
Karen
K
Messer
Thomas J
TJ
Kipps
Paul A
PA
Insel
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013997:Time Factors; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; C517463:PDE7B protein, human