Abstract 4881

We have recently shown that NB4,an APL cell line, is dependent on glycolysis, while THP-1, a monocytic cell line, is relatively dependent on oxidative phosphorylation in mitochondria, where oxidation of fatty acid is important. (Leukemia and Lymphoma 51:2112,2010)

Here, we examined the energy metabolism of these leukemia cell lines in immunodeficient mice. 1.0×107 cells of each cell line were inoculated subcutaneously in NOD/scid mice with the treatment of anti-asialo GM1 antibody. Mice were divided into two groups: normal diet (carbohydrate;65.3%, fat;6.3%) or carbohydrate-restricted (high fat) diet (carbohydrate;19.6%, fat;62.2%). At day 42, tumor volume (TV) of NB4 in three normal diet-fed mice became 694±358mm3, which was greater than that in three high fat diet-fed mice:173±216mm3 (P= 0.043). On the other hand, tumor volume of THP-1 in three normal diet-fed mice became 1130 ± 600mm3, which was smaller than that in three high fat diet-fed mice: 3300 ± 1053mm3 (p = 0.050).

Then, since 14 days after inoculation of leukemia cells in NOD/scid mice fed with normal diet, glycolysis inhibitor 2-deoxy-D-glucose (2-DG) (35mg/mouse) was administered intraperitoneally once a week. Tumor size at day 41 of both leukemia cells were suppressed by 2-DG treatment. (THP-1: 2-DG (-): TV = 3099 ± 193mm3, 2-DG (+): TV = 513 ± 550mm3) (THP-1: p = 0.040). (NB4: 2-DG (-): TV = 495 ± 417mm3, 2-DG (+): TV = 87 ± 89mm3) (NB4: p = 0.313).

Pathological examination of tumors have shown that 2-DG treated tumor had larger areas of dead cells in both cell lines.

Our study demonstrated that NB4 is dependent largely on glucose and THP-1 on fat. In addition, 2-DG is effective in growth suppression of leukemia cells in vivo. These findings will help the future therapy for leukemia targeting energy metabolism.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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