Prognostic significance of Tie-1 protein expression in patients with early chronic phase chronic myeloid leukemia.
BACKGROUND
The Tie-1 tyrosine kinase receptor and its thus far unidentified ligand appear to play a distinct role in the regulatory pathways of early hematopoiesis and angiogenesis. Because vascularity is increased in the bone marrow of patients with chronic myeloid leukemia (CML), the authors evaluated the clinical significance of Tie-1 expression in such patients.


METHODS
Using Western blot analysis and solid-phase radioimmunoassay (RIA), the authors quantified Tie-1 protein in bone marrow samples from 128 patients with CML and 31 normal controls.


RESULTS
The median Tie-1 RIA value of CML samples was significantly higher than in normal controls (P = 0.01). The authors found no significant differences in Tie-1 levels in patients with early chronic, late chronic, accelerated, and blastic phases (P = 0.2). High Tie-1 levels correlated with short survival in patients with early chronic phase (P = 0.003; Cox proportional hazard model) but not in patients with late chronic (P = 0.2) or accelerated/blastic (P = 0.2) phase CML. Tie-1 protein level was also prognostic when patients were separated into two groups by the median value. High Tie-1 level in early chronic phase was associated with significantly shorter survival than low Tie-1 level (median survival, 116 vs. 61 months; P = 0.03). In patients with early chronic phase CML, Tie-1 levels correlated directly with patient age (P = 0.004) and platelet count (P = 0.003), and inversely with leukocyte count (P = 0.007). Tie-1 as a predictor of survival in early chronic phase CML was independent of risk group, spleen size, age, hemoglobin, and basophil count (P = 0.03; multivariate Cox proportional hazard model).


CONCLUSIONS
The authors' findings support the hypothesis that angiogenesis may play a major role in the pathophysiology of chronic phase CML.
Verstovsek
Srdan
S
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Kantarjian
Hagop
H
Manshouri
Taghi
T
O'Brien
Susan
S
Faderl
Stefan
S
Talpaz
Moshe
M
Cortes
Jorge
J
Albitar
Maher
M
D000368:Aged; D015153:Blotting, Western; D001853:Bone Marrow / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D011863:Radioimmunoassay; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D042810:Receptor, TIE-1; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D042764:Receptors, TIE; D012307:Risk Factors; D016019:Survival Analysis
D011956:Receptors, Cell Surface; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042764:Receptors, TIE