# ACTION OF RETINOIDS ON MYELOID LEUKEMIA

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1990 · $63,177

## Abstract

Retinoic acid and its analogs (retinoids) enhance normal human
muyelopoiesis 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.  One approach to the therapy of leukemia is the induction
of differentiation of the neoplastic cells.  A number of new retinoids
have been recently synthesized; some of these compounds are 10-100 fold
more potent than all-trans retinoic acid in several non-hematopoietic
assays.  We will test the potency of new retinoids on clonal growth and
induction of differentiation of normal and neoplastic human myeloid
progenitor cells in vitro.  Agents that appear to be effective in vitro
will be tested against leukemic cells in vivo in the murine subcapsular
renal assay and in nude mice.  2. The mechanism of action of retinoids is
not understood.  Recently, the retinoic acid receptor (RAR) cDNA has been
isolated.  We will use the RAR cDNA in an expression vector in
combination with RAR antibodies and RAR protein as tools to study the
biological role RAR has in normal and neoplastic hematopoietic cells.  3.
We shall isolate and study the gene(s) that encodes for novel protein(s)
made by T-lymphocytes which induce differentiation of leukemic cells.
The gene(s) shall be isolated by a unique expression system.  Such
factor(s) will be very important for studying the regulation of
hematopoiesis and their implication for possibly treating some leukemias
is clear.  4. We shall determine the clinical significance of ras
mutations in leukemia and preleukkemia.  This study will be possible
because of the marriage of three recent advances:  1) polymerase chain
reaction; 2) Taq polymerase; 3) ability to isolate useful DNA from
formaldehyde-fixed, paraffin embedded bone marrow specimens.  We will
examine for ras mutations in the DNA from several 1000 samples for which
we already have the clinical data of the patients.  This knowledge may
give insights into the pathogenesis of some leukemias and may allow
better sub-classification of leukemias and preleukemias.  As a whole, the
studies will provide an understanding of both the process of normal
myeloid differentiation and the defect in differentiation of blast cells
in some leukemias.  Our findings may have clinical applications for
certain leukemias.

## Key facts

- **NIH application ID:** 3171683
- **Project number:** 5R01CA033936-08
- **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:** 1990
- **Award amount:** $63,177
- **Award type:** 5
- **Project period:** 1983-02-01 → 1994-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171683

## Citation

> US National Institutes of Health, RePORTER application 3171683, ACTION OF RETINOIDS ON MYELOID LEUKEMIA (5R01CA033936-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171683. Licensed CC0.

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