# WHITE BLOOD CELL OXIDASE IN LEUKEMIA AND NORMAL CELLS

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 1988 · $246,840

## Abstract

The overall purpose of this project is to examine the development
and regulation superoxide-generating oxidase in phagocytic
leukocytes.  Studies performed in the first grant period (1983-86)
delineated the cell physiology and enzymology of superoxide
production during induced differentiation of the HL-60 human
promelocytic leukemia cell line and in various forms of chronic
granulomatous disease (CGD).  During the next five years, the
proposed studies will extend to the molecular level of regulation
of the oxidase.  The major tool for these experiments is
complementary DNA (cDNA) from the recently cloned gene
(termed "X-CGD") for X-linked CGD.  The specific aims of the
project are:  I. Examination of X-CGD gene expression during
induced differentiation of HL-60 cells.  This section will focus on
the steady state levels and rates of synthesis and degradation of
X-CGD transcripts (using techniques of blot and solution
hybridization, nuclear transcriptional run-off, and 32p pulse-chase
labelling).  Other studies in HL-60 will explore the role of the cell
cycle in X-CGD expression and the effects of introduction of the
full-length cDNA linked to differentiation-independent promoters.
II. Examination of X-CGD gene expression in differentiating
myeloid precursors derived from normal human bone marrow.
These studies, utilizing myeloid cells in culture and mixed bone
marrow cells in situ, will parallel those in HL-60 in order to verify
the findings in non-leukemic cells.  III. Examination of X-CGD
gene expression in granulocytes and macrophages treated with
cytokines that modulate superoxide production.  These studies will
determine the effects of human recombinant interferon gamma,
tumor necrosis factor, and granulocytes-macrophage colony-
stimulating factor on X-CGD transcript levels and kinetics.  IV.
Application of these studies to CGD.  These studies will extend
preliminary results on the effects of IFN-gamma on CGD
phagocytes, develop and refine methods for the prenatal diagnosis
of CGD, and determine the molecular nature of genetic defects
that cause the disease.  V. Probes for other oxidase components
will be obtained or cloned from HL-60 libraries to complement
the studies with X-CGD.  As these probes become available, they
will be used to similarly study the regulation of other genes
contributing to oxidase activity.  Overall, this project is intended
both to increase our understanding and to indicate means of
therapeutic manipulation of a vital arm of host defense.

## Key facts

- **NIH application ID:** 3176397
- **Project number:** 5R01CA038325-05
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **SAM.gov UEI:** MQE2JHHJW9Q8
- **Principal Investigator:** PETER E NEWBURGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $246,840
- **Award type:** 5
- **Project period:** 1984-07-01 → 1992-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176397

## Citation

> US National Institutes of Health, RePORTER application 3176397, WHITE BLOOD CELL OXIDASE IN LEUKEMIA AND NORMAL CELLS (5R01CA038325-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176397. Licensed CC0.

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