The level of glycolytic metabolism in acute myeloid leukemia blasts at diagnosis is prognostic for clinical outcome

被引:89
作者
Herst, Patries M. [3 ]
Howman, Rebecca A. [1 ]
Neeson, Paul J. [2 ]
Berridge, Michael V. [3 ]
Ritchie, David S. [1 ,2 ,4 ]
机构
[1] Peter MacCallum Canc Ctr, Div Haematol & Med Oncol, Melbourne, Vic 8006, Australia
[2] Peter MacCallum Canc Ctr, Div Res, Canc Immunol Program, Melbourne, Vic 8006, Australia
[3] Malaghan Inst Med Res, Wellington, New Zealand
[4] Univ Melbourne, Parkville, Vic 3052, Australia
关键词
glucose; chemotherapy; remission; survival; INDUCED APOPTOSIS; RESISTANCE; CELLS;
D O I
10.1189/jlb.0710417
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
This research investigated the level of glycolytic metabolism in leukemic blasts as a prognostic marker in AML. Using an in vitro dye-reduction assay, we determined the level of glycolytic metabolism in 26 BM samples taken from 23 adult patients with newly diagnosed (n=19) or relapsed (n=4) AML, and AML blasts stratified into two distinct cohorts of moderate (<70%) or high (>80%) levels of glycolytic metabolism. All samples taken at relapse were moderately glycolytic. However, nine of the 19 samples taken at diagnosis were highly glycolytic, and 10 were moderately glycolytic. Three patients had paired samples taken at diagnosis and relapse, and the glycolytic metabolism of these samples did not alter between the two time-points. The level of glycolytic metabolism did not correlate with the percentage of marrow blasts, patient age, or CG/molecular risk group. Highly glycolytic AML blasts were more resistant to apoptosis induced by ATRA and/or ATO in vitro, suggesting potential resistance to induction chemotherapy, as has been observed in solid tumors. Despite this, high levels of glycolytic metabolism at diagnosis were predictive of a significantly improved duration of CR1 and OS following AML remission induction chemotherapy. In conclusion, we found that the extent of myeloblast glycolysis may be an effective and easily applied method to determine the pretreatment prognosis of AML. J. Leukoc. Biol. 89: 51-55; 2011.
引用
收藏
页码:51 / 55
页数:5
相关论文
共 12 条
  • [1] Age and acute myeloid leukemia
    Appelbaum, FR
    Gundacker, H
    Head, DR
    Slovak, ML
    Willman, CL
    Godwin, JE
    Anderson, JE
    Petersdorf, SH
    [J]. BLOOD, 2006, 107 (09) : 3481 - 3485
  • [2] Glucocorticoid resistance in T-lineage acute lymphoblastic leukaemia is associated with a proliferative metabolism
    Beesley, A. H.
    Firth, M. J.
    Ford, J.
    Weller, R. E.
    Freitas, J. R.
    Perera, K. U.
    Kees, U. R.
    [J]. BRITISH JOURNAL OF CANCER, 2009, 100 (12) : 1926 - 1936
  • [3] RETRACTED: Increase sensitivity to chemotherapeutical agents and cytoplasmatic interaction between NPM leukemic mutant and NF-κB in AML carrying NPM1 mutations (Retracted article. See vol. 24, pg. 1103, 2010)
    Cilloni, D.
    Messa, F.
    Rosso, V.
    Arruga, F.
    Defilippi, I.
    Carturan, S.
    Catalano, R.
    Pautasso, M.
    Panuzzo, C.
    Nicoli, P.
    Messa, E.
    Morotti, A.
    Iacobucci, I.
    Martinelli, G.
    Bracco, E.
    Saglio, G.
    [J]. LEUKEMIA, 2008, 22 (06) : 1234 - 1240
  • [4] Why do cancers have high aerobic glycolysis?
    Gatenby, RA
    Gillies, RJ
    [J]. NATURE REVIEWS CANCER, 2004, 4 (11) : 891 - 899
  • [5] Glycolytic metabolism confers resistance to combined all-trans retinoic acid and arsenic trioxide-induced apoptosis in HL60ρ0 cells
    Herst, Patries A.
    Hesketh, Elizabeth L.
    Ritchie, David S.
    Berridge, Michael V.
    [J]. LEUKEMIA RESEARCH, 2008, 32 (02) : 327 - 333
  • [6] Cell surface oxygen consumption: A major contributor to cellular oxygen consumption in glycolytic cancer cell lines
    Herst, Patries M.
    Berridge, Michael V.
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2007, 1767 (02): : 170 - 177
  • [7] Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells
    Hulleman, Esther
    Kazemier, Karin M.
    Holleman, Amy
    VanderWeele, David J.
    Rudin, Charles M.
    Broekhuis, Mathilde J. C.
    Evans, William E.
    Pieters, Rob
    Den Boer, Monique L.
    [J]. BLOOD, 2009, 113 (09) : 2014 - 2021
  • [8] NONPARAMETRIC-ESTIMATION FROM INCOMPLETE OBSERVATIONS
    KAPLAN, EL
    MEIER, P
    [J]. JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1958, 53 (282) : 457 - 481
  • [9] Legrand O, 2004, HAEMATOLOGICA, V89, P34
  • [10] Negative regulation of p53 by nucleophosmin antagonizes stress-induced apoptosis in human normal and malignant hematopoietic cells
    Li, J
    Zhang, XL
    Sejas, DP
    Pang, QS
    [J]. LEUKEMIA RESEARCH, 2005, 29 (12) : 1415 - 1423