# ACTION OF RETINOIDS ON MYELOID LEUKEMIA CELLS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1987 · $49,078

## Abstract

Retinoic acid and its analogs (retinoids) stimulate normal human
myelopoiesis and erythropoiesis, and inhibit leukemic blast cell clonal
proliferation and induce differentiation of leukemic blast cells in vitro.
The phenotypic abnormality of human acute myelogenous leukemia is the
inability of the leukemic cells to differentiate to functional,
non-dividing cells.  Preleukemia is a hematopoietic syndrome that preceeds
leukemia; the leukemic clone is often established and abnormalities of
differentiation are predominant in this disease.  The only standard therapy
for these patients is supportive.  One approach to the therapy of
preleukemia (and leukemia) is the induction of differentiation of the
neoplastic cells.  We are conducting a double blind, randomized trial of
administering 13-cis retinoic versus placebo to 80 preleukemia patients in
order to determine if the therapy improves their hematopoiesis decreases
the size of their neoplastic clone (as determined by karyotypic
examinations), and possibly alters the course of their disease.  A number
of new retinoids have recently been synthesized; these compounds are
10-1000 fold more potent than all trans retinoic acid in several
non-hematopoietic assays of inhibition of transformation.  We will test the
potency of these compounds on clonal growth and induction of
differentiation of normal and neoplastic human myeloid progenitor cells in
vitro.  Treatment of cancer patients with chemotherapy has clearly taught
us that a combination of agents is frequently more efficiacious than
treatment with a single drug.  We shall identify and study compounds that
interact synergistically with retinoids to decrease proliferation of
leukemia cells and/or to enhance differentiation of leukemia cells.  Agents
that appear to be effective in vitro frequently are ineffective in vivo.
We shall try to develop a murine model to study the effect of retinoids on
proliferation of leukemia cells in vivo.  Retinoids alter expression of
several oncogenes in HL-60 myeloid leukemic cells; we shall examine
alterations of chromatin and nuclear matrix in the vicinity of these
oncogenes in HL-60 cells exposed to retinoids.  An understanding of the
process of myeloid differentiation may provide the framework to understand
the defect in differentiation of blast cells in leukemia.

## Key facts

- **NIH application ID:** 3171681
- **Project number:** 5R01CA033936-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **SAM.gov UEI:** RN64EPNH8JC6
- **Principal Investigator:** Harold Phillip Koeffler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $49,078
- **Award type:** 5
- **Project period:** 1983-02-01 → 1989-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171681

## Citation

> US National Institutes of Health, RePORTER application 3171681, ACTION OF RETINOIDS ON MYELOID LEUKEMIA CELLS (5R01CA033936-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171681. Licensed CC0.

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