title: Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia.
abstract: The aim of this study was to evaluate the possible prognostic relevance of thymidine kinase serum levels (s-TK), an indirect marker of proliferative activity, in myelodysplastic syndromes (MDS). S-TK levels were monitored by means of a radioenzyme assay in 90 patients affected by MDS (22 refractory anaemia, RA; 17 RA with ring sideroblasts, RARS; 21 RA with blast excess, RAEB; 15 RAEB in transformation, RAEB-T; 15 chronic myelomonocytic leukaemia, CMMoL). Mean s-TK levels (U/microliter) measured at diagnosis were 11.9 +/- 12.6 for RA, 11.4 +/- 13.6 for RARS, 19.9 +/- 28.4 for RAEB, 39.6 +/- 34.3 for RAEB-T and 77.7 +/- 69.7 for CMMoL (normal values < 5 U/microliter). With the only exception of a weak relationship with lactate dehydrogenase, no correlation was found between initial s-TK values and other clinical or laboratory parameters, such as age, haemoglobin, white blood cell or platelet count, percentage of bone marrow blasts. MDS patients with s-TK > 38 U/microliters, a cut-off level selected by means of ROC statistical analysis, showed a significantly shorter survival than those with s-TK < 38 U/microliter (8.2 v 37.4 months, respectively; P < 0.0001). In particular, transformation in acute myeloid leukaemia (AML) occurred in 17/21 (81%) of patients with s-TK > 38 U/microliters and 9/69 (13%) of those with lower levels at diagnosis (P < 0.0001), independently of FAB subtype. High s-TK levels were also useful to predict evolution in AML during the course of the disease in patients with normal initial values. Multivariate analysis confirmed the independent prognostic value of s-TK on both overall survival and risk of acute transformation. We conclude that s-TK may be an important prognostic factor in MDS, strongly correlated with development of AML.
authors.affiliation: Division of Haematology, IRCCS Casa Sollievo della Sofferenza Hospital, S. Giovanni Rotondo, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Musto
authors.forename: C
authors.initials: C
authors.lastname: Bodenizza
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: G
authors.initials: G
authors.lastname: D'Arena
authors.forename: P
authors.initials: P
authors.lastname: Scalzulli
authors.forename: G
authors.initials: G
authors.lastname: Perla
authors.forename: S
authors.initials: S
authors.lastname: Modoni
authors.forename: L
authors.initials: L
authors.lastname: Parlatore
authors.forename: M R
authors.initials: MR
authors.lastname: Valvano
authors.forename: M
authors.initials: M
authors.lastname: Carotenuto
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007951:Leukemia, Myeloid / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000201:enzymology*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D013937:Thymidine Kinase / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D013937:Thymidine Kinase