Serum pseudouridine in the diagnosis of acute leukaemias and as a novel prognostic indicator in acute lymphoblastic leukaemia.
The serum level of pseudouridine, a modified nucleoside deriving mainly from t-RNA catabolism, was evaluated in 66 acute leukaemia patients at diagnosis to investigate its diagnostic and prognostic value, and its potential as a parameter with which to classify subtypes of the disease. Serum pseudouridine, measured by high performance liquid chromatography, was increased in acute lymphoblastic leukaemia patients (90% according to the pseudouridine index, which is the serum pseudouridine/creatinine ratio), and in acute myeloblastic leukaemia patients (75% according to the pseudouridine index). The increase was higher in the L3 than in the L1 and L2 subtypes. In the acute lymphoblastic leukaemia group there was a highly significant inverse correlation between serum pseudouridine levels and the most common end-point parameters used to assess disease outcome in leukaemia (i.e., complete remission rate, disease-free survival, and overall survival). In addition, 83% of patients with serum pseudouridine values < 5.5 nmol/mL were alive and in complete remission 12 months after the initial diagnosis, while only 11% of patients with serum pseudouridine values > 5.5 nmol/mL were alive and none were disease-free after the same period. This study: 1. demonstrates that the diagnostic sensitivity of the pseudouridine index is high in adult acute lymphoblastic leukaemia and good in acute myeloblastic leukaemia; 2. suggests that the serum pseudouridine assay can contribute to the classification of adult acute lymphoblastic leukaemia; and 3. demonstrates unequivocally that both pseudouridine assay and the pseudouridine index are excellent independent prognostic markers for acute lymphoblastic leukaemia.
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Dipartimento di Biochimica e Biotechnologie Mediche, CEINGE Centro Ingegneria Genetica, Naples, Italy.
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D011560:Pseudouridine / Q000097:blood*; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011560:Pseudouridine