Table 1 Possible mechanisms by which leukemic stem cells survive after ARA-C treatment and approaches to optimize therapy

Survival mechanisms

leukemic cell survival

References

12-h interval between ARA-C infusions too long

reduce interval

[16]

deficiency in CdR kinase

3-DU + ARA-C

[20–22]

increase in dCTP

3-DU + ARA-C

[20–22]

increase CR deaminase

THU + ARA-C

[24, 25]

CR deaminase inactivation of ARA-C in liver

THU + ARA-C

[24, 25]

block in cell cycle progression G1 to S phase

intermittent ARA-C, DAC

[30]

high frequency of leukemic stem cells

3-DU + ARA-C, DAC prime ARA-C

[22, 36]

resistance to apoptosis

DAC prime ARA-C, DAC

[36, 40]