Relation of 5′-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia

R. Pieters; D. R. Huismans; A. H. Loonen; G. J. Peters; K. Hählen; A. van der Does-van den Berg; E. R. van Wering; A. J.P. Veerman

doi:10.1016/0145-2126(92)90033-4

Relation of 5′-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia

R. Pieters, D. R. Huismans, A. H. Loonen, G. J. Peters, K. Hählen, A. van der Does-van den Berg, E. R. van Wering, A. J.P. Veerman

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

Abstract

Ecto-5′-nucleotidase (ecto-5′NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5′NT (cyto-5′NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5′NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10 cμ^- precursor B-ALL. CD10⁺ ALL cases with high ecto-5′NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5′NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5′NT and AP activities. We conclude that high ecto-5′NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5′NT and AP activities associated with 6-thiopurine resistance.

Original language	English
Pages (from-to)	873-880
Number of pages	8
Journal	Leukemia Research
Volume	16
Issue number	9
DOIs	https://doi.org/10.1016/0145-2126(92)90033-4
Publication status	Published - Sept 1992
Externally published	Yes

Keywords

5′nucleotidase
childhood leukemia
drug resistance
IMPase
MTT assay
phosphatase
prognosis
purine metabolism
thiopurines

Access to Document

10.1016/0145-2126(92)90033-4

Cite this

Pieters, R., Huismans, D. R., Loonen, A. H., Peters, G. J., Hählen, K., van der Does-van den Berg, A., van Wering, E. R., & Veerman, A. J. P. (1992). Relation of 5′-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia. Leukemia Research, 16(9), 873-880. https://doi.org/10.1016/0145-2126(92)90033-4

@article{53faa17f3c8b466fb1ae9345ae1ab971,

title = "Relation of 5′-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia",

abstract = "Ecto-5′-nucleotidase (ecto-5′NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5′NT (cyto-5′NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5′NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10 cμ- precursor B-ALL. CD10+ ALL cases with high ecto-5′NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5′NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5′NT and AP activities. We conclude that high ecto-5′NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5′NT and AP activities associated with 6-thiopurine resistance.",

keywords = "5′nucleotidase, childhood leukemia, drug resistance, IMPase, MTT assay, phosphatase, prognosis, purine metabolism, thiopurines",

author = "R. Pieters and Huismans, {D. R.} and Loonen, {A. H.} and Peters, {G. J.} and K. H{\"a}hlen and {van der Does-van den Berg}, A. and {van Wering}, {E. R.} and Veerman, {A. J.P.}",

note = "Funding Information: NUCLEOTIDASES catalyze the dephosphorylation of purine nucleotides like GMP, IMP and AMP to their corresponding nucleosides guanosine, inosine and adenosine respectively. Ecto-5'nucleotidase (ecto-5'NT) is localized on the cell membrane with the enzymatic activity facing the external medium. Its function involves extracellular dephosphorylation of nucleotides to which cells are impermeable, into readily transported nucleosides \[1-5\]. The intracellular degradation of nucleotides is most probably not regulated by ecto-5'NT but by cytoplasmic 5'NT (cyto-5'NT) and by non-specific phosphatases like acid-and alkaline phosphatases (AP). Cyto-5'NT is biochemically distinguishable from ecto-5'NT \[6-8\] because of a different pH optimum (6.0 vs 7.4-9.0 respectively). Also, a~,fl-methylene adenosine dipho- * Supported by the Dutch Cancer Society (IKA 87-17). Correspondence to: R. Pieters, M.D., Ph.D., M.Sc., Free University Hospital, Department of Pediatrics, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.",

year = "1992",

month = sep,

doi = "10.1016/0145-2126(92)90033-4",

language = "English",

volume = "16",

pages = "873--880",

journal = "Leukemia Research",

issn = "0145-2126",

publisher = "Elsevier Ltd.",

number = "9",

}

TY - JOUR

T1 - Relation of 5′-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia

AU - Pieters, R.

AU - Huismans, D. R.

AU - Loonen, A. H.

AU - Peters, G. J.

AU - Hählen, K.

AU - van der Does-van den Berg, A.

AU - van Wering, E. R.

AU - Veerman, A. J.P.

N1 - Funding Information: NUCLEOTIDASES catalyze the dephosphorylation of purine nucleotides like GMP, IMP and AMP to their corresponding nucleosides guanosine, inosine and adenosine respectively. Ecto-5'nucleotidase (ecto-5'NT) is localized on the cell membrane with the enzymatic activity facing the external medium. Its function involves extracellular dephosphorylation of nucleotides to which cells are impermeable, into readily transported nucleosides \[1-5\]. The intracellular degradation of nucleotides is most probably not regulated by ecto-5'NT but by cytoplasmic 5'NT (cyto-5'NT) and by non-specific phosphatases like acid-and alkaline phosphatases (AP). Cyto-5'NT is biochemically distinguishable from ecto-5'NT \[6-8\] because of a different pH optimum (6.0 vs 7.4-9.0 respectively). Also, a~,fl-methylene adenosine dipho- * Supported by the Dutch Cancer Society (IKA 87-17). Correspondence to: R. Pieters, M.D., Ph.D., M.Sc., Free University Hospital, Department of Pediatrics, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

PY - 1992/9

Y1 - 1992/9

N2 - Ecto-5′-nucleotidase (ecto-5′NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5′NT (cyto-5′NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5′NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10 cμ- precursor B-ALL. CD10+ ALL cases with high ecto-5′NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5′NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5′NT and AP activities. We conclude that high ecto-5′NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5′NT and AP activities associated with 6-thiopurine resistance.

AB - Ecto-5′-nucleotidase (ecto-5′NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5′NT (cyto-5′NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5′NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10 cμ- precursor B-ALL. CD10+ ALL cases with high ecto-5′NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5′NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5′NT and AP activities. We conclude that high ecto-5′NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5′NT and AP activities associated with 6-thiopurine resistance.

KW - 5′nucleotidase

KW - childhood leukemia

KW - drug resistance

KW - IMPase

KW - MTT assay

KW - phosphatase

KW - prognosis

KW - purine metabolism

KW - thiopurines

UR - http://www.scopus.com/inward/record.url?scp=0026806087&partnerID=8YFLogxK

U2 - 10.1016/0145-2126(92)90033-4

DO - 10.1016/0145-2126(92)90033-4

M3 - Article

C2 - 1405718

AN - SCOPUS:0026806087

SN - 0145-2126

VL - 16

SP - 873

EP - 880

JO - Leukemia Research

JF - Leukemia Research

IS - 9

ER -

Relation of 5′-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia

Abstract

Keywords

Access to Document

Fingerprint

Cite this