Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human promyelocytic leukemia cell line HL-60 undergoes terminal myeloid differentiation in vitro in response to a wide variety of chemicals. The tumor promoter phorbol myristate acetate induces these cells to develop macrophage-like morphology, adherence, and enzymatic characteristics. The present study confirms those observations and further documents the induction, by 16 nM phorbol myristate acetate, of 5'-nucleotidase activity, another human macrophage marker enzyme. However, more importantly, functional studies show that phorbol myristate acetate-induced HL-60 cells fail to increase above base line uninduced levels of hexose monophosphate shunt activity, superoxide generation, nitroblue tetrazolium reduction, bacterial ingestion, or complement secretion. These cells therefore possess some macrophage-like properties but do not meet several important functional criteria of macrophage identity.
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PMID:Functionally deficient differentiation of HL-60 promyelocytic leukemia cells induced by phorbol myristate acetate. 626 Mar 53

Cross-resistance patterns between chemotherapeutic agents have implications for the treatment of hematologic and other diseases. Previous in vitro models have shown cross-resistance between the purine analog 2-chlorodeoxyadenosine (cladribine) and the pyrimidine analogs 2',2'-difluorodeoxycytidine (gemcitabine) and 1-beta-D-arabinofuranosylcytosine (cytosine arabinoside, cytarabine) with reduced deoxycytidine kinase (dCK) activity as the underlying determinant of resistance. In this study, we continuously exposed the human promyelocytic leukemia cell line HL60 to as much as 1024 nM cladribine. After limiting dilution, the cladribine concentrations that caused 50% growth inhibition (IC50) of the two clones R13 and R23 were 33.3- and 18.7-fold, respectively, higher than the IC50 of the parental HL60 cells (8.7+/-1.3 nM). These cladribine-resistant clones, however, showed no cross-resistance to gemcitabine and only 3.3- and 2.7-fold resistance to cytarabine, respectively. Characterization of both clones revealed stably elevated levels of purine-specific "high-Michaelis constant (Km)" 5'-nucleotidase (5'-NT) messenger RNA expression and specific activity, whereas pyrimidine-specific "low-Km" 5'-NT activity was undetectable, and dCK activity was only marginally decreased in R13. Thus, the ratio of dCK (specific for cladribine) to high-Km 5'-NT activity in R13 and R23 was reduced to 65.3% and 63.7%, respectively. These results show that changes of high-Km 5'-NT activity can induce cladribine resistance, without cross-resistance to gemcitabine.
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PMID:Lack of cross-resistance with gemcitabine and cytarabine in cladribine-resistant HL60 cells with elevated 5'-nucleotidase activity. 984 78