AT-101 induces apoptosis in CLL B cells and overcomes stromal cell-mediated Mcl-1 induction and drug resistance

Blood

Volumn 113, Issue 1, 2009, Pages 149-153

  Balakrishnan, Kumudha ^a,b   Burger, Jan A ^b   Wierda, William G ^b   Gandhi, Varsha ^a,b  

^a Departments of Experimental Therapeutics and Leukemia

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLUDARABINE; ISOSORBIDE; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN KINASE B; PROTEIN MCL 1; ANTINEOPLASTIC AGENT; DRUG DERIVATIVE; GOSSYPOL; GOSSYPOL ACETIC ACID; MYELOID CELL LEUKEMIA SEQUENCE 1 PROTEIN; PROTEIN BCL 2; VIDARABINE;

APOPTOSIS; ARTICLE; B LYMPHOCYTE; CANCER RESISTANCE; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVATION; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; LYMPHOCYTE; MICROENVIRONMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; STROMA CELL; CELL COMMUNICATION; CYTOLOGY; DOSE RESPONSE; DRUG EFFECT; DRUG RESISTANCE; METABOLISM; PATHOLOGY; TUMOR CELL CULTURE;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; B-LYMPHOCYTES; CELL COMMUNICATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; DRUG RESISTANCE, NEOPLASM; GOSSYPOL; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; PROTO-ONCOGENE PROTEINS C-BCL-2; STROMAL CELLS; TUMOR CELLS, CULTURED; VIDARABINE;

EID: 59449095496     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2008-02-138560     Document Type: Article

References (25)

1. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005;352:804-815.
2. Schimmer AD, Munk-Pedersen I, Minden MD, Reed JC. Bcl-2 and apoptosis in chronic lymphocytic leukemia. Curr Treat Options Oncol. 2003;4: 211-218.
3. Hanada M, Delia D, Aiello A, Stadtmauer E, Reed JC. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood. 1993;82:1820-1828.
4. Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102:13944-13949.
5. Kitada S, Andersen J, Akar S, et al. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with In vitro and In vivo chemoresponses. Blood. 1998;91:3379-3389.
6. Longo PG, Laurenti L, Gobessi S, Sica S, Leone G, Efremov DG. The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood. 2008;111:846-855.
7. Burger M, Hartmann T, Krome M, et al. Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells. Blood. 2005;106:1824-1830.
8. Collins RJ, Verschuer LA, Harmon BV, Prentice RL, Pope JH, Kerr JF. Spontaneous programmed death (apoptosis) of B-chronic lymphocytic leukaemia cells following their culture in vitro. Br J Haematol. 1989;71:343-350.
9. Panayiotidis P, Jones D, Ganeshaguru K, Foroni L, Hoffbrand AV. Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro. Br J Haematol. 1996;92:97-103.
10. Caligaris-Cappio F. Role of the microenvironment in chronic lymphocytic leukaemia. Br J Haematol. 2003;123:380-388.
11. Nishio M, Endo T, Tsukada N, et al. Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1alpha. Blood. 2005;106:1012-1020.
12. Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps TJ. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cellderived factor-1. Blood. 2000;96:2655-2663.
13. Pedersen IM, Kitada S, Leoni LM, et al. Protection of CLL B cells by a follicular dendritic cell line is dependent on induction of Mcl-1. Blood. 2002; 100:1795-1801.
14. Mudry RE, Fortney JE, York T, Hall BM, Gibson LF. Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy. Blood. 2000; 96:1926-1932.
15. Balakrishnan K, Wierda WG, Keating MJ, Gandhi V. Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells. Blood. 2008; 112:1971-1980.
16. Oltersdorf T, Elmore SW, Shoemaker AR, et al.An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435:677-681.
17. Del Gaizo Moore V, Brown JR, Certo M, Love TM, Novina CD, Letai A. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT- 737. J Clin Invest. 2007;117:112-121.
18. Paoluzzi L, Gonen M, Gardner JR, et al. Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma. Blood. 2008;111: 5350-5358.
19. Saleh MPH, Hartung J, Holmlund J, LoBuglio A, Forero A. Phase I trial of AT-101, an orally bioavailable inhibitor of Bcl-2, in patients with advanced malignancies. AACR-NCI-EORTC International Conference. 2005;(suppl)3:220.
20. Loberg RD, McGregor N, Ying C, Sargent E, Pienta KJ. In vivo evaluation of AT-101 (R-(-)- gossypol acetic acid) in androgen-independent growth of VCaP prostate cancer cells in combination with surgical castration. Neoplasia. 2007;9: 1030-1037.
21. Castro JE LO, Aguillon RA, et al. A phase II, open label study of AT-101 in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. Blood. 2006;108: 803a.
22. James DF MR, Mosadeghi R, Kipps TJ. AT-101, a pan-inhibitor of Bcl-2 family anti-apoptotic proteins, antagonizes the protective effect conferred by nurse-like cells on primary chronic lymphocytic leukemia cells. Blood. 2006;108:595a.
23. Balakrishnan K, Nimmanapalli R, Ravandi F, Keating MJ, Gandhi V. Forodesine, an inhibitor of purine nucleoside phosphorylase, induces apoptosis in chronic lymphocytic leukemia cells. Blood. 2006;108:2392-2398.
24. Pepper C, Lin TT, Pratt G, et al. Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers. Blood. 2008;112:3807-3817.
25. Barragan M, Bellosillo B, Campas C, Colomer D, Pons G, Gil J. Involvement of protein kinase C and phosphatidylinositol 3-kinase pathways in the survival of B-cell chronic lymphocytic leukemia cells. Blood. 2002;99:2969-2976.