p53/Surviving Ratio as a Parameter for Chemotherapy Induction Response in Children with Acute Myeloid Leukemia


  • Rinaldi Lenggana Brawijaya university
  • Susanto Nugroho Brawijaya University
  • Sri Winarsih Saiful Anwar Public Hospital




p53, surviving, acute myeloid leukemia


Acute myeloid leukemia (AML) is a malignancy that is often found in children. Many studies into the failure of apoptosis function, or programmed cell death, is one of the most important regulatory mechanisms of cellular hemostasis which is closely linked to the development of cancer, are important. Also, regulation of the apoptotic (p53) and anti-apoptotic (surviving) proteins influence treatment outcome. One role of p53 is to monitor cellular stress necessary to induce apoptosis. Surviving (BIRC5) is a group of proteins in the apoptosis inhibitor which works by inhibiting caspase-3. The role of surviving is considered very important in oncogenesis proliferation and cell growth regulation. Chemotherapy in childhood AML can inhibit cell growth and induce slowing as well as stopping the cell cycle. Thus, the aim of this study was to compare p53 and surviving before and after receiving induction chemotherapy in children with AML and also to determine the p53/surviving ratio. Peripheral blood mononuclear cells were collected from AML children before treatment and three months after starting their induction therapy. p53 and surviving were measured by flowcytometry using monoclonal antibodies. Data were analyzed by t-test for comparison between groups and Spearman’s test to find out the correlation between variables with a significant value of p < 0.05. A total of 8 children were evaluated. The intensity of p53 expression was not significantly increased after induction phase chemotherapy (p = 0.224), but surviving expression and the ratio of p53/surviving were significantly increased in the treatment group compared with the levels prior to chemotherapy (p = 0.002, p = 0.034), and there was a strong negative correlation between p53 and surviving after chemotherapy (r = −0.63, p = 0.049).

Author Biography

Rinaldi Lenggana, Brawijaya university

pediatric health, brawijaya universitymagister of biomedical, brawijaya university


Gaynon P.S. Childhood acute myeloid leukemia and relaps. British J Haematol, 13, 2005, 579-87.

Spector L.G., Ross J.A., Robison L.L. Epidemiology and etiology in childhood leukemias (New York: Cambridge University Press, 2006) 48-61.

Pui C.H., Robinson L.L., Look A.T. Acute myeloid leukemia. Lancet. 371, 2008,1030-43.

Ribera J.M.and Oriol A. Acute myeloid leukemia in adolescents and young adults. Hematol Oncol Clin North Am, 23(5), 2009, 1033- 42.

Ross D.D. Novel mechanisms of drug resistance in leukemia. Leukemia, 14, 2000, 467-473.

MacKenzie S.H.and Clark A.C. Targeting cell death in tumors by activating caspases. Current cancer drug targets, 8, 2008,98-109.

Altieri D.C. Survivin and IAP proteins in cell death mechanisms. Biochem J. 430, 2010, 199-205.

Schimmer A.D., Pedersen I.M., Kitada S., et al. Functional blocks in caspase activation pathways are common in leukemia and predict patient response to induction chemotherapy. Cancer Res. 63, 2003, 1242-48.

Fulda S. And Debatin K.M. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 25, 2006, 4798-811.

Dohi T., Okada K., Xia F., et al. An IAP-IAP complex inhibits apoptosis. J Biol Chem, 279 (33), 2004, 34087-34090.

Carter B.Z., Wang R.Y., Schober W.D., Milella M., Andreeff M. Targeting survivin expression induces cell proliferasion defect and subsequent celldeath involving mitochondrial pathway in myeloid leukemic cell. Cell cycle, 2 (5), 2003, 488-493.

Esh A.M., Atfy M., Azizi N.A., El Naggar M.M.,Khalil E.E., Sherief L. Prognostic Significance of survivin in Pediatric Acute Lymphoblastic Leukemia.Indian J Hematol Blood Transfusion, 27(1), 2011, 18-25.

Prokop A., Wieder T., Sturm I., Mann F.E., Seeger K., Wuchter C., et al. Relaps in childhood acute lymphoblastic leukemia is associated with a decrease of the Bax/Bcl-2 ratio and loss of spontaneous caspase-3 processing in vivo. Leukemia. 14, 2000, 1606-13.

Mulatsih S. Fusi gena TEL-AML1, BCR-ABL, E2A-PPBX1, dan MLL-AF4 sebagai faktor prognosis leukemia limfoblastik akut (Fakultas Kedokteran Universitas Gadjah Mada Yogyakarta. 2009).

Biondi, Cazzaniaga, Masera. New stratification of childhood acute lymphoblastic leukemia. Hematology,1, 2005, 133-7.

Holleman A., Boer M.L., Kazemier M.R., Janka-Schaub G.E., Pieters R. Resistance to different classes of drugs is associated with impaired apoptosis in childhood acute lymphoblastic leukemia. Blood Journal Hematology,102, 2003, 4541-4546.

Faderl S., Thall P.F., Kantarjian H.M., Talpaz M., Haris D., Van Q., et al. Caspase-2 and Caspase-3 as predictors of complete remission and survival in adults with acute myeloid leukemia. Clin Cancer Res.5, 1999, 4041-47.

Meyer L.H., Karawajew L., Schrappe M., Ludwig W.D., Debatin K.M. and Stahnke K. Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL. Blood, 2008, 4524-31.

Ghavami S., Hashemi M., Ande S.R., et al. 2009. Apoptosis and cancer: mutations within caspase Genes. J Med Genet., 46, 2009, 497–510.

Lu Y.and Chen G.Q. Effector caspases and leukemia. Int J Cell Biology. 10, 2011, 1-8.

Fulda S. 2009. Therapeutic opportunities for counteracting apoptosis resistance in childhood leukemia. British J Haematol. 145, 2009, 441-54.

Miura M, Chen X.D., et al. 2004. A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells. Journal of Clinical Investigation. 114(12), 2004, 1704-1713.

Darzynkiewicz Z.,Huang X., Okafuji M.,King M.,A. Cytometric methods to detect apoptosis. Methods cell biology, 75, 2004, 307-341.

Liu T., Raetz E., Moss P.J., Perkins S.L., Bruggers C.S., Smith F., Carroll W.L. Diversity of the apoptotic response to chemotheraphy in childhood leukemia. Leukemia. 16, 2002, 223 – 232.

alama M.A., Hassab H.M., Gendy W.E., Zeid M.Y. Study of caspase-3 level in relation to prognostic risk factors in children with acute myeloid leukemia. Alexandria Journal of Pediatrics. 19(1), 2005, 45-49.

Soung YH, Lee JW, Kim SY, Park WS, Nam SW, Lee JY, Yoo NJ, Lee SH. Somatic mutations of CASP3 gene in human cancers. Hum Genet., 115, 2004, 112–5.

Shin S., Sung B.J., Cho Y.S., Kim H.J., Ha N.C.,Hwang J.I., et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry, 40, 2001, 1117-23.

Tamm I., Richter S., Oltersdorf D., Creutzig U., Harbott J., Scholz F., et al. High expression levels of x-linked inhibitor of apoptosis protein and survivin correlate with poor overall survival in childhood de novo acute myeloid leukemia. Clin Cancer Res.10, 2004, 3737-44. The Expression of Caspase-3 and Survivin Related with Induction Chemotherapy in Childhood Acute www.iosrjournals.org 29 | Page

Vogler M., Giagkousiklidis S., Genze F., Gschwend J.E., Debatin K.M., Fulda S. Inhibition of clonogenic tumor growth: a novel function of smac contributing to its antitumor activity. Oncogene. 24, 2005, 7190-202.

Fortugno P., Wall N.R., Giodini A., O’Connor D.S., Plescia J, Padgett KM.,et al. Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function. J Cell Sci, 115, 2002, 575–585

Park E., Eun J.G.,Hsieh Y.T.,Schaeffer P., Chae S., Klemm L., et al. Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia. Blood, 118(8), 2011, 2191-2199.

Zhou M., Gu L., Li F., Zhu Y., Woods W.G., Findley H.W. DNA damage induces a novel p53-survivin signaling pathway regulating cell cycle and apoptosis in acute myeloid leukemia cells. J Pharmacol Exp Therapy, 303, 2002, 124-31.

Troeger A., Siepermann M., Escherich G., Meisel R., Willers R., Gudowius S., et al. Survivin and its prognostic significance in pediatric acute B-cell precursor myeloid leukemia. Hematologica, the hematology Journal, 92 (8), 2007, 1043.

Yahya R.S., Fouda M.I., El Baz H.A., Mosa T.E., Maksoud M.D.A. Serum survivin and TP 53 gene expression in children with acute myeloid leukemia. Iranian J Publ Health, 41(1), 2012, 37-44.