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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1922-1926
NEOPLASIA
Expression of high Km 5'-nucleotidase in leukemic blasts is an
independent prognostic factor in adults with acute myeloid
leukemia
Carlos M. Galmarini,
Kathryn Graham,
Xavier Thomas,
Fabien Calvo,
Philippe Rousselot,
Assia El
Jafaari,
Emeline Cros,
John R. Mackey, and
Charles Dumontet
From the Unité INSERM 453-Laboratoire de
Cytologie Analytique, Faculté de Médécine
Rockefeller, Lyon, France; Cross Cancer Institute, Edmonton, Canada;
Service d'Hématologie, Hôpital Edouard Herriot, Lyon,
France; Service d'Hématologie, Hôpital Saint Louis, Paris,
France; and Centre de Transfusion, Hôpital Edouard Herriot, Lyon,
France.
Cytarabine (ara-C) requires activation into its triphosphorylated
form, ara-CTP, to exert cytotoxic activity. Cytoplasmic 5'-nucleotidase
(5NT) dephosphorylates ara-CMP, a key intermediate, preventing
accumulation of ara-CTP and may reduce cellular sensitivity to the
cytotoxic activity of ara-C. To determine whether the level of
expression of 5NT is correlated with clinical outcome in patients with
acute myeloid leukemia (AML) treated with ara-C, this study analyzed
the levels of messenger RNA expression of high Km 5NT by real-time
polymerase chain reaction at diagnosis in blast cells of 108 patients
with AML. High Km 5NT was expressed at diagnosis in the blast cells of
54% of patients. In univariate analysis, (1) patients whose blast
cells contained high levels (values greater than the median value for
total population) of high Km 5NT at diagnosis had significantly shorter
disease-free survival (DFS) than patients with low levels of high Km
5NT (11 months versus 17.5 months, P = .02) and (2) high
levels of high Km 5NT also predicted significantly shorter overall
survival (15.7 months versus 39 months, P = .01) in young
patients ( 57 years; median value for the entire population). In a
multivariate analysis taking into account age, karyotype risk, and
other factors found to have prognostic significance in univariate
analysis, (1) high Km 5NT expression was an independent prognostic
factor for DFS and (2) high levels of high Km 5NT also predicted
significantly shorter overall survival in young patients. These results
demonstrate that the expression of high levels of high Km 5NT in blast
cells is correlated with outcome in patients with AML.
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