Induction of white cell proliferation due to haematopoietic growth factors is associated with an increase in multiple forms of dihydrofolate reductase in non-neutropenic cancer patients

M. P. Iqbal, I. A. Burney, F. Sultana, N. Mehboobali

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) are frequently used in cancer patients to overcome the granulocytopenic effects of chemotherapy, and also to mobilize the stem cells. The mobilized stem cells are collected from the peripheral blood and used for transplantation following high doses of chemotherapy. However, the molecular mechanism by which these colony stimulating factors (CSFs) bring about proliferation of myeloid precursor cells is not clearly known. Dihydrofolate reductase (DHFR), which has an established role in DNA synthesis, could be a link between administration of CSF and stem cell proliferation. The purpose of this study was to investigate whether CSFs induce white cell proliferation by producing multiple forms of DHFR. Methods: Twelve patients with non-haematological malignancies were treated with either G-CSF or GM-CSF to mobilize stem cells. Nine healthy subjects were treated with placebo as controls. Blood samples were obtained before and after stimulation with CSFs or placebo. White blood cells were separated and concentrations of both active DHFR and immunoreactive nonfunctional form of DHFR were determined in their cytoplasm using methotrexate-binding assay and enzyme-linked immunosorbent assay, respectively. Total leucocytes count (TLC) was also monitored before and after stimulation with CSFs or placebo. Results: There was a significant (P<0.05) increase in concentration of immunoreactive nonfunctional form of DHFR and TLC following stimulation with CSFs. There was an increase in concentration of active DHFR as well, however, this did not reach statistical significance. In the placebo-treated subjects, no significant increase in active DHFR, immunoreactive nonfunctional form of enzyme or TLC was observed. However, it was noticed that the base-line values of active DHFR and immunoreactive nonfunctional form of enzyme in leucocytes of cancer patients were higher than the base-line values in leukocytes of normal healthy subjects. Conclusion: Our data suggest that colony stimulating factors induce white cell proliferation by increasing levels of multiple forms of DHFR.

Original languageEnglish
Pages (from-to)68-71
Number of pages4
JournalJournal of the Pakistan Medical Association
Volume51
Issue number2
Publication statusPublished - Feb 2001

Fingerprint

Tetrahydrofolate Dehydrogenase
Colony-Stimulating Factors
Intercellular Signaling Peptides and Proteins
Cell Proliferation
Neoplasms
Leukocyte Count
Placebos
Leukocytes
Stem Cells
Granulocyte Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Healthy Volunteers
Drug Therapy
Myeloid Cells
Enzymes
Methotrexate
Cytoplasm
Transplantation
Enzyme-Linked Immunosorbent Assay
DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{09571ecd3b1d4b91b3fa580d8ce30aa8,
title = "Induction of white cell proliferation due to haematopoietic growth factors is associated with an increase in multiple forms of dihydrofolate reductase in non-neutropenic cancer patients",
abstract = "Objective: Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) are frequently used in cancer patients to overcome the granulocytopenic effects of chemotherapy, and also to mobilize the stem cells. The mobilized stem cells are collected from the peripheral blood and used for transplantation following high doses of chemotherapy. However, the molecular mechanism by which these colony stimulating factors (CSFs) bring about proliferation of myeloid precursor cells is not clearly known. Dihydrofolate reductase (DHFR), which has an established role in DNA synthesis, could be a link between administration of CSF and stem cell proliferation. The purpose of this study was to investigate whether CSFs induce white cell proliferation by producing multiple forms of DHFR. Methods: Twelve patients with non-haematological malignancies were treated with either G-CSF or GM-CSF to mobilize stem cells. Nine healthy subjects were treated with placebo as controls. Blood samples were obtained before and after stimulation with CSFs or placebo. White blood cells were separated and concentrations of both active DHFR and immunoreactive nonfunctional form of DHFR were determined in their cytoplasm using methotrexate-binding assay and enzyme-linked immunosorbent assay, respectively. Total leucocytes count (TLC) was also monitored before and after stimulation with CSFs or placebo. Results: There was a significant (P<0.05) increase in concentration of immunoreactive nonfunctional form of DHFR and TLC following stimulation with CSFs. There was an increase in concentration of active DHFR as well, however, this did not reach statistical significance. In the placebo-treated subjects, no significant increase in active DHFR, immunoreactive nonfunctional form of enzyme or TLC was observed. However, it was noticed that the base-line values of active DHFR and immunoreactive nonfunctional form of enzyme in leucocytes of cancer patients were higher than the base-line values in leukocytes of normal healthy subjects. Conclusion: Our data suggest that colony stimulating factors induce white cell proliferation by increasing levels of multiple forms of DHFR.",
author = "Iqbal, {M. P.} and Burney, {I. A.} and F. Sultana and N. Mehboobali",
year = "2001",
month = "2",
language = "English",
volume = "51",
pages = "68--71",
journal = "JPMA. The Journal of the Pakistan Medical Association",
issn = "0030-9982",
publisher = "Pakistan Medical Association",
number = "2",

}

TY - JOUR

T1 - Induction of white cell proliferation due to haematopoietic growth factors is associated with an increase in multiple forms of dihydrofolate reductase in non-neutropenic cancer patients

AU - Iqbal, M. P.

AU - Burney, I. A.

AU - Sultana, F.

AU - Mehboobali, N.

PY - 2001/2

Y1 - 2001/2

N2 - Objective: Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) are frequently used in cancer patients to overcome the granulocytopenic effects of chemotherapy, and also to mobilize the stem cells. The mobilized stem cells are collected from the peripheral blood and used for transplantation following high doses of chemotherapy. However, the molecular mechanism by which these colony stimulating factors (CSFs) bring about proliferation of myeloid precursor cells is not clearly known. Dihydrofolate reductase (DHFR), which has an established role in DNA synthesis, could be a link between administration of CSF and stem cell proliferation. The purpose of this study was to investigate whether CSFs induce white cell proliferation by producing multiple forms of DHFR. Methods: Twelve patients with non-haematological malignancies were treated with either G-CSF or GM-CSF to mobilize stem cells. Nine healthy subjects were treated with placebo as controls. Blood samples were obtained before and after stimulation with CSFs or placebo. White blood cells were separated and concentrations of both active DHFR and immunoreactive nonfunctional form of DHFR were determined in their cytoplasm using methotrexate-binding assay and enzyme-linked immunosorbent assay, respectively. Total leucocytes count (TLC) was also monitored before and after stimulation with CSFs or placebo. Results: There was a significant (P<0.05) increase in concentration of immunoreactive nonfunctional form of DHFR and TLC following stimulation with CSFs. There was an increase in concentration of active DHFR as well, however, this did not reach statistical significance. In the placebo-treated subjects, no significant increase in active DHFR, immunoreactive nonfunctional form of enzyme or TLC was observed. However, it was noticed that the base-line values of active DHFR and immunoreactive nonfunctional form of enzyme in leucocytes of cancer patients were higher than the base-line values in leukocytes of normal healthy subjects. Conclusion: Our data suggest that colony stimulating factors induce white cell proliferation by increasing levels of multiple forms of DHFR.

AB - Objective: Granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) are frequently used in cancer patients to overcome the granulocytopenic effects of chemotherapy, and also to mobilize the stem cells. The mobilized stem cells are collected from the peripheral blood and used for transplantation following high doses of chemotherapy. However, the molecular mechanism by which these colony stimulating factors (CSFs) bring about proliferation of myeloid precursor cells is not clearly known. Dihydrofolate reductase (DHFR), which has an established role in DNA synthesis, could be a link between administration of CSF and stem cell proliferation. The purpose of this study was to investigate whether CSFs induce white cell proliferation by producing multiple forms of DHFR. Methods: Twelve patients with non-haematological malignancies were treated with either G-CSF or GM-CSF to mobilize stem cells. Nine healthy subjects were treated with placebo as controls. Blood samples were obtained before and after stimulation with CSFs or placebo. White blood cells were separated and concentrations of both active DHFR and immunoreactive nonfunctional form of DHFR were determined in their cytoplasm using methotrexate-binding assay and enzyme-linked immunosorbent assay, respectively. Total leucocytes count (TLC) was also monitored before and after stimulation with CSFs or placebo. Results: There was a significant (P<0.05) increase in concentration of immunoreactive nonfunctional form of DHFR and TLC following stimulation with CSFs. There was an increase in concentration of active DHFR as well, however, this did not reach statistical significance. In the placebo-treated subjects, no significant increase in active DHFR, immunoreactive nonfunctional form of enzyme or TLC was observed. However, it was noticed that the base-line values of active DHFR and immunoreactive nonfunctional form of enzyme in leucocytes of cancer patients were higher than the base-line values in leukocytes of normal healthy subjects. Conclusion: Our data suggest that colony stimulating factors induce white cell proliferation by increasing levels of multiple forms of DHFR.

UR - http://www.scopus.com/inward/record.url?scp=0035033261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035033261&partnerID=8YFLogxK

M3 - Article

VL - 51

SP - 68

EP - 71

JO - JPMA. The Journal of the Pakistan Medical Association

JF - JPMA. The Journal of the Pakistan Medical Association

SN - 0030-9982

IS - 2

ER -