We tested to what extent preincubation with the ribonucleotide reductase inhibitors fludarabine ( F-ara-A ) and hydroxyurea ( HU ) enhanced ara-CTP levels in two human myeloid ( HL-60 , CMK ) and two lymphoblastic leukemia cell lines ( MOLT-4 , BLIN-1 ) and also in blasts from 28 children with acute leukemia ( AML : 14 , ALL : 14 ) .
Modulation of ara-CTP levels by fludarabine and hydroxyurea in leukemic cells. The rate of ara-cytosine triphosphate (ara-CTP) accumulation and its retention has been correlated with 1-beta-D-arabinofuranosylcytosine (ara-C)-mediated toxicity and clinical outcome in childhood and adult leukemia. We tested to what extent preincubation with the ribonucleotide reductase inhibitors fludarabine ( F-ara-A ) and hydroxyurea ( HU ) enhanced ara-CTP levels in two human myeloid ( HL-60 , CMK ) and two lymphoblastic leukemia cell lines ( MOLT-4 , BLIN-1 ) and also in blasts from 28 children with acute leukemia ( AML : 14 , ALL : 14 ) . Incubation experiments carried out with cell lines showed F-ara-A and HU to be equipotent in increasing ara-CTP levels. The highest increase was observed in HL-60 cells whereas preincubation had no modulatory effect in MOLT-4 cells. Accordingly, modulation of intracellular ara-CTP levels differed between the subtypes of childhood acute leukemia: whereas in T-ALL (five) preincubation with F-ara-A and HU had no effect on intracellular ara-C metabolism, increased ara-CTP levels were seen in some cases of pre-B-ALL (seven). In myelogenous blasts (12) clinically relevant enhancement of ara-C toxification was regularly obtained with both, F-ara-A (1.9-fold) and HU (1.5-fold). In conclusion, our data suggest that combinations of ara-C and ribonucleotide reductase inhibitors are apt to increase ara-CTP levels depending on the individual cell type and its sensitivity towards ara-C modulators.
### Instruction:
            Given the context about compound efficacy for the given treatment mentioned within the input, mentioned the compounds 
            that can co-occur for the mentioned treatment

            ### Input:
            Modulation of ara-CTP levels by fludarabine and hydroxyurea in leukemic cells. The rate of ara-cytosine triphosphate (ara-CTP) accumulation and its retention has been correlated with 1-beta-D-arabinofuranosylcytosine (ara-C)-mediated toxicity and clinical outcome in childhood and adult leukemia. We tested to what extent preincubation with the ribonucleotide reductase inhibitors fludarabine ( F-ara-A ) and hydroxyurea ( HU ) enhanced ara-CTP levels in two human myeloid ( HL-60 , CMK ) and two lymphoblastic leukemia cell lines ( MOLT-4 , BLIN-1 ) and also in blasts from 28 children with acute leukemia ( AML : 14 , ALL : 14 ) . Incubation experiments carried out with cell lines showed F-ara-A and HU to be equipotent in increasing ara-CTP levels. The highest increase was observed in HL-60 cells whereas preincubation had no modulatory effect in MOLT-4 cells. Accordingly, modulation of intracellular ara-CTP levels differed between the subtypes of childhood acute leukemia: whereas in T-ALL (five) preincubation with F-ara-A and HU had no effect on intracellular ara-C metabolism, increased ara-CTP levels were seen in some cases of pre-B-ALL (seven). In myelogenous blasts (12) clinically relevant enhancement of ara-C toxification was regularly obtained with both, F-ara-A (1.9-fold) and HU (1.5-fold). In conclusion, our data suggest that combinations of ara-C and ribonucleotide reductase inhibitors are apt to increase ara-CTP levels depending on the individual cell type and its sensitivity towards ara-C modulators.

            ### Response:
            fludarabine, hydroxyurea
            