Cancer Procoagulant in Acute Non Lymphoid Leukemia: Relationship of Enzyme Detection to Disease Activity^[*]

Summary

Blast cell extracts from patients with acute non lymphoid leukemia (ANLL) express cancer procoagulant (cp). Thii factor X (FX) activator is distinct from tissue factor (TF) in that it does not require factor VII (FVII) to trigger blood coagulation, it acts as a cysteine proteinase and is not present in normal mononuclear cells. Tb assess whether there is any relationship between the presence of CP and the status of the disease, ANLL patients have been studied at diagnosis, during remission, at relapse. The procoagulant activity in either the presence or absence of F VII and sensitivity to cysteine proteinaie inhibitors were tested on cell extracts. Immunoreactivity was explored with an anti-cP polyclonal antibody. Data obtained in gL newlydiagnosed ANLL patients (subtypes M1 to M5, EAB classification) confirmed the presence of cp in M1- to M4 groups (mean + sE Fvll-independent activity: M1 = 2.1 ± 0.7 unit/mg; M2 = 5.7 ± 1.7 unit/mg; M3 = 31.5 ± 8 unit/mg M4 = 1.6 ± 1.2 unit/mg; CP was absent in the M5 type. In eight patients analy zedin a subsequent phase of partial remission, specific activity had dropped from 26.9 ± 7.8 to 10.5 ± 4.0 unit/mg. Activiiy was virtually absent (0−0.05 unit/mg) in the bone marrow of 37 patients studied at complete remission. Bone marrow samples from six subjects tested at different intervals after complete remission were repeatedly negative for CP but became positive 2 to 5 months before relapse. Upon relapse, the FVII indbpendent activity rose to 24.2 ± 8.2 unit/mg.

These results suggest that CP activity may be closely associated with the presence of myeloid malignant cells in the bone marrow, a finding of potential relevance not only to the coagulation disorders of acute leukemia, but also to the early deteition of blast cells in ANLL.

• References

• 1 Rasche H, Dietrich M. Hemostatic abnormalities associated with malignant diseases. Eur J Cancer 1977; 13: 1053-1064
• 2 Donati MB, Poggi A, Semeraro N. Coagulation and malignancy. In: Recent Advances in Blood Coagulation Poller L. (ed). Raven Press; 1981: 227-259
• 3 Gralnick HR, Marchesi S, Givelberg H. Intravascular coagulation in acute leukemia: Clinical and subclinical abnormalities. Blood 1972; 40: 709-718
• 4 Myers TJ, Rickies FR, Barb C, Cronlund M. Fibrinopeptide A in acute leukemia: Relationship of activation of blood coagulation to disease activity. Blood 1981; 57: 518-525
• 5 Gralnick HR, Sultan C. Acute promyelocytic leukemia: Haemor-rhagic manifestations and morphologic criteria. Br J Haematol 1975; 29: 373-376
• 6 Nemerson Y. Tissue factor and hemostasis. Blood 1988; 71: 1-8
• 7 Van de Water L, Tracy PB, Aronson D, Mann KG, Dvorak HF. Tumor cell generation of thrombin via prothrombinase assembly. Cancer Res 1985; 45: 5521-5525
• 8 Falanga A, Gordon SG. Isolation and characterization of cancer procoagulant: A cysteine proteinase from malignant tissue. Biochemistry 1985; 24: 5558-5567
• 9 Falanga A, Alessio MG, Donati MB, Barbui T. A new procoagulant in acute leukemia. Blood 1988; 71: 870-875
• 10 Bennett JM, Catowsky D, Daniel MT. et al Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British cooperative group. Ann Intern Med 1985; 103: 626-629
• 11 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of dye-binding. Anal Biochem 1976; 72: 248-254
• 12 Gordon SG, Cross BA. A factor X activating cysteine protease from malignant tissue. J Clin Invest 1981; 67: 1665-1671
• 13 Falanga A, Shaw E, Donati MB, Consonni R, Barbui T, Gordon SG. Inhibition of cancer procoagulant by peptidyl diazomethyl ketones and peptidyl sulfonium salts. Thromb Res 1989; 54: 389-398
• 14 Curatolo L, Colucci M, Cambini AL, Poggi A, Morasca L, Donati MB, Semeraro N. Evidence that cells from experimental tumors can activate coagulation factor X. Br J Cancer 1979; 40: 228-233
• 15 Gordon SG, Franks JJ, Lewis BJ. Comparison of procoagulants in extracts of normal and malignant human tissue. J Natl Cancer Inst 1979; 62: 773-779
• 16 Gordon SG, Gilbert LC, Lewis BJ. Analysis of procoagulant activity of intact cells from tissue culture. Thromb Res 1982; 26: 379-387
• 17 Donati MB, Gambacorti PasseriniC, Casali B, Falanga A, Vannotti P, Fossati G, Semeraro N, Gordon SG. Cancer procoagulant in human tumor cells: Evidence from melanoma patients. Cancer Res 1986; 46: 6471-6474
• 18 Grignani G, Falanga A, Pacchiarini L, Alessio MG, Zucchella M, Fratino P, Donati MB. Human breast and colon carcinomas express cysteine proteinase activities with pro-aggregating and procoagulant properties. Int J Cancer 1988; 42: 554-557
• 19 Gordon SG, Hiashiba U, Cross BA, Poole MA, Falanga A. A cysteine proteinase procoagulant from amnion-chorion. Blood 1985; 66: 1261-1265
• 20 Falanga A, Gordon SG. Comparison of properties of cancer procoagulant and human amnion-chorion procoagulant. Biochim Biophys Acta 1985; 831: 161-165
• 21 Alessio MG, Falanga A, Consonni R, Bassan R, Minetti B, Donati MB, Barbui T. Cancer procoagulant in acute lymphoblastic leukemia. Eur J Haematol 1990 in press
• 22 Andoh K, Kubota T, Takada M, Tanaka H, Kobayashi N, Maekawa T. Tissue factor activity in leukemia cells. Cancer 1987; 59: 748-754
• 23 Guarini A, Gugliotta L, Catani L, Chetti L, Macchi S, Tura S. Procoagulant cellular activity (PCA) in the classification of acute leukemia. Thromb Res 1987; 45: 545-552
• 24 Borin L, Lanzafame C, Baldicchi L, Gambacorti PasseriniG, Pogliani E, Corneo G. Cancer procoagulant activity as marker in a case of early cutaneous relapse of promyelocytic leukemia. In: Infections and Haemorrhage in Acute Leukaemia Barbui T. et al. (eds). John Libbey Eurotext; Paris: 1989: 33-36