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Chemical Compound Review

Leukeran     4-[4-[bis(2-chloroethyl) amino]phenyl]butan...

Synonyms: Amboclorin, Chlorbutin, Lympholysin, chlorambucil, NSC-3088, ...
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Disease relevance of NSC-3088


Psychiatry related information on NSC-3088


High impact information on NSC-3088


Chemical compound and disease context of NSC-3088


Biological context of NSC-3088

  • Chlorambucil-induced chromosome damage to human lymphocytes [15].
  • The high frequency of deletions and translocations among the mutations induced in post-spermatogonial stages by chlorambucil, combined with its overall high efficiency in inducing mutations in these stages, should make chlorambucil mutagenesis useful for generating experimentally valuable germ-line deletions throughout the mouse genome [16].
  • Thus far, all but one of the tested mutations induced by chlorambucil in post-stem-cell stages have been proved deletions or other structural changes by genetic, cytogenetic, and/or molecular criteria [17].
  • Chlorambucil-induced mutations in mice recovered in homozygotes [18].
  • Intact plasma depleted of albumin by chromatography on Cibacron blue-Sepharose or plasma from a subject with analbuminemia failed either to activate AKT or to protect CLL cells from chlorambucil-induced apoptosis [19].

Anatomical context of NSC-3088


Associations of NSC-3088 with other chemical compounds


Gene context of NSC-3088

  • However, when the BL-bcl-2 cells were treated with CMB together with ligation of CD40, apoptosis was reduced further to only 17% at 96 h [27].
  • Cells overexpressing GSTM1 displayed a 3- to 4-fold increase in resistance to anticancer drugs vincristine (VCR) and chlorambucil (CHB) in proliferation, cytotoxic, and clonogenic survival assays [28].
  • Increased mdr1/P-glycoprotein mRNA levels were also found in relapsed state acute myelogenous leukaemias (AML), and in chronic lymphocytic leukaemias (CLL) treated with chlorambucil and/or prednisone for several years [29].
  • MRP2 was able to support GSTA1-1-mediated resistance to chlorambucil (CHB) cytotoxicity in HepG2 cells [30].
  • The aim of this study was to evaluate the prognostic impact of CD38 expression by peripheral blood lymphocytes on progression-free survival after first-line therapy with high-dose chlorambucil in 53 previously untreated patients affected by typical CD5+ CD23+ B-CLL [31].

Analytical, diagnostic and therapeutic context of NSC-3088


  1. Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. Dighiero, G., Maloum, K., Desablens, B., Cazin, B., Navarro, M., Leblay, R., Leporrier, M., Jaubert, J., Lepeu, G., Dreyfus, B., Binet, J.L., Travade, P. N. Engl. J. Med. (1998) [Pubmed]
  2. Long-term evaluation of chlorambucil plus prednisone in the idiopathic nephrotic syndrome of childhood. Williams, S.A., Makker, S.P., Ingelfinger, J.R., Grupe, W.E. N. Engl. J. Med. (1980) [Pubmed]
  3. Chlorambucil treatment of frequently relapsing nephrotic syndrome. Grupe, W.E., Makker, S.P., Ingelfinger, J.R. N. Engl. J. Med. (1976) [Pubmed]
  4. A randomized trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. Ponticelli, C., Zucchelli, P., Passerini, P., Cagnoli, L., Cesana, B., Pozzi, C., Pasquali, S., Imbasciati, E., Grassi, C., Redaelli, B. N. Engl. J. Med. (1989) [Pubmed]
  5. Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. Berk, P.D., Goldberg, J.D., Silverstein, M.N., Weinfeld, A., Donovan, P.B., Ellis, J.T., Landaw, S.A., Laszlo, J., Najean, Y., Pisciotta, A.V., Wasserman, L.R. N. Engl. J. Med. (1981) [Pubmed]
  6. Critical prenatal periods for chlorambucil-induced functional alterations of the rat kidney. Kavlock, R.J., Rehnberg, B.F., Rogers, E.H. Toxicology (1987) [Pubmed]
  7. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. Rai, K.R., Peterson, B.L., Appelbaum, F.R., Kolitz, J., Elias, L., Shepherd, L., Hines, J., Threatte, G.A., Larson, R.A., Cheson, B.D., Schiffer, C.A. N. Engl. J. Med. (2000) [Pubmed]
  8. Methylprednisolone plus chlorambucil as compared with methylprednisolone alone for the treatment of idiopathic membranous nephropathy. The Italian Idiopathic Membranous Nephropathy Treatment Study Group. Ponticelli, C., Zucchelli, P., Passerini, P., Cesana, B. N. Engl. J. Med. (1992) [Pubmed]
  9. Controlled trial of methylprednisolone and chlorambucil in idiopathic membranous nephropathy. Ponticelli, C., Zucchelli, P., Imbasciati, E., Cagnoli, L., Pozzi, C., Passerini, P., Grassi, C., Limido, D., Pasquali, S., Volpini, T. N. Engl. J. Med. (1984) [Pubmed]
  10. Specific targeting of chlorambucil to tumors with the use of monoclonal antibodies. Smyth, M.J., Pietersz, G.A., Classon, B.J., McKenzie, I.F. J. Natl. Cancer Inst. (1986) [Pubmed]
  11. Prednisolone and chlorambucil treatment in idiopathic membranous nephropathy with deteriorating renal function. Mathieson, P.W., Turner, A.N., Maidment, C.G., Evans, D.J., Rees, A.J. Lancet (1988) [Pubmed]
  12. Randomised trial comparing low-dose cisplatin and chlorambucil with low-dose cisplatin, chlorambucil, and doxorubicin in advanced ovarian carcinoma. Barker, G.H., Wiltshaw, E. Lancet (1981) [Pubmed]
  13. Multicentric reticulohistiocytosis: response to alkylating agents in six patients. Ginsburg, W.W., O'Duffy, J.D., Morris, J.L., Huston, K.A. Ann. Intern. Med. (1989) [Pubmed]
  14. Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial. Robak, T., Bloński, J.Z., Kasznicki, M., Blasińska-Morawiec, M., Krykowski, E., Dmoszyńska, A., Mrugala-Spiewak, H., Skotnicki, A.B., Nowak, W., Konopka, L., Ceglarek, B., Maj, S., Dwilewicz-Trojaczek, J., Hellmann, A., Urasiński, I., Zdziarska, B., Kotlarek-Haus, S., Potoczek, S., Grieb, P. Blood (2000) [Pubmed]
  15. Chlorambucil-induced chromosome damage to human lymphocytes. Palmer, R.G., Dore, C., Denman, A.M. Lancet (1985) [Pubmed]
  16. Genetic and molecular analysis of chlorambucil-induced germ-line mutations in the mouse. Rinchik, E.M., Bangham, J.W., Hunsicker, P.R., Cacheiro, N.L., Kwon, B.S., Jackson, I.J., Russell, L.B. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  17. Chlorambucil effectively induces deletion mutations in mouse germ cells. Russell, L.B., Hunsicker, P.R., Cacheiro, N.L., Bangham, J.W., Russell, W.L., Shelby, M.D. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  18. Chlorambucil-induced mutations in mice recovered in homozygotes. Flaherty, L., Messer, A., Russell, L.B., Rinchik, E.M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  19. Albumin activates the AKT signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis. Jones, D.T., Ganeshaguru, K., Anderson, R.J., Jackson, T.R., Bruckdorfer, K.R., Low, S.Y., Palmqvist, L., Prentice, H.G., Hoffbrand, A.V., Mehta, A.B., Wickremasinghe, R.G. Blood (2003) [Pubmed]
  20. Wegener's granulomatosis, lymphomatoid granulomatosis, and benign lymphocytic angiitis and granulomatosis of lung. Recognition and treatment. Israel, H.L., Patchefsky, A.S., Saldana, M.J. Ann. Intern. Med. (1977) [Pubmed]
  21. Chemosensitivity of lymphocytes from patients with B-cell chronic lymphocytic leukemia to chlorambucil, fludarabine, and camptothecin analogs. Silber, R., Degar, B., Costin, D., Newcomb, E.W., Mani, M., Rosenberg, C.R., Morse, L., Drygas, J.C., Canellakis, Z.N., Potmesil, M. Blood (1994) [Pubmed]
  22. Glutathione depletion in chronic lymphocytic leukemia B lymphocytes. Silber, R., Farber, C.M., Papadopoulos, E., Nevrla, D., Liebes, L., Bruck, M., Brown, R., Canellakis, Z.N. Blood (1992) [Pubmed]
  23. Overexpression of metallothionein confers resistance to anticancer drugs. Kelley, S.L., Basu, A., Teicher, B.A., Hacker, M.P., Hamer, D.H., Lazo, J.S. Science (1988) [Pubmed]
  24. Treatment of Bechçet's syndrome with transfer factor. Wolf, R.E., Fudenberg, H.H., Welch, T.M., Spitler, L.E., Ziff, M. JAMA (1977) [Pubmed]
  25. Lectin derivatives of methotrexate and chlorambucil as chemotherapeutic agents. Lin, J.Y., Li, J.S., Tung, T.C. J. Natl. Cancer Inst. (1981) [Pubmed]
  26. Theophylline synergizes with chlorambucil in inducing apoptosis of B-chronic lymphocytic leukemia cells. Mentz, F., Mossalayi, M.D., Ouaaz, F., Baudet, S., Issaly, F., Ktorza, S., Semichon, M., Binet, J.L., Merle-Beral, H. Blood (1996) [Pubmed]
  27. Germinal center-derived signals act with Bcl-2 to decrease apoptosis and increase clonogenicity of drug-treated human B lymphoma cells. Walker, A., Taylor, S.T., Hickman, J.A., Dive, C. Cancer Res. (1997) [Pubmed]
  28. Glutathione S-transferase M1 and multidrug resistance protein 1 act in synergy to protect melanoma cells from vincristine effects. Depeille, P., Cuq, P., Mary, S., Passagne, I., Evrard, A., Cupissol, D., Vian, L. Mol. Pharmacol. (2004) [Pubmed]
  29. Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase pi gene expression in primary and relapsed state adult and childhood leukaemias. Gekeler, V., Frese, G., Noller, A., Handgretinger, R., Wilisch, A., Schmidt, H., Muller, C.P., Dopfer, R., Klingebiel, T., Diddens, H. Br. J. Cancer (1992) [Pubmed]
  30. Role of multidrug resistance protein 2 (MRP2, ABCC2) in alkylating agent detoxification: MRP2 potentiates glutathione S-transferase A1-1-mediated resistance to chlorambucil cytotoxicity. Smitherman, P.K., Townsend, A.J., Kute, T.E., Morrow, C.S. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  31. Peripheral blood CD38 expression predicts time to progression in B-cell chronic lymphocytic leukemia after first-line therapy with high-dose chlorambucil. Morabito, F., Mangiola, M., Stelitano, C., Deaglio, S., Callea, V., Malavasi, F. Haematologica (2002) [Pubmed]
  32. Failure of second-look laparotomy to influence survival in epithelial ovarian cancer. Luesley, D., Lawton, F., Blackledge, G., Hilton, C., Kelly, K., Rollason, T., Wade-Evans, T., Jordan, J., Fielding, J., Latief, T. Lancet (1988) [Pubmed]
  33. Association of acute leukaemia with chlorambucil after renal transplantation. Ho, W.K., Robertson, M.R., Macdonald, G.J., Charlesworth, J.A., Pussell, B.A. Lancet (1994) [Pubmed]
  34. Chlorambucil therapy in hairy cell leukemia: effects on lipid composition and lymphocyte subpopulations. Krigel, R., Liebes, L.F., Pelle, E., Silber, R. Blood (1982) [Pubmed]
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