Expression of high Km 5'-nucleotidase in leukemic blasts is an independent prognostic factor in adults with acute myeloid leukemia.
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 (< or = 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.
Galmarini
C M
CM
Unité INSERM 453-Laboratoire de Cytologie Analytique, Faculté de Médécine Rockefeller, Lyon, France. fgalma@rockefeller.univ-lyon1.fr
Graham
K
K
Thomas
X
X
Calvo
F
F
Rousselot
P
P
El Jafaari
A
A
Cros
E
E
Mackey
J R
JR
Dumontet
C
C
D015720:5'-Nucleotidase / Q000096:biosynthesis* / Q000235:genetics; D000208:Acute Disease; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014158:Transcription, Genetic; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D012334:RNA, Neoplasm; D003561:Cytarabine; D015720:5'-Nucleotidase