# CELL CYCLE SPECIFIC CONTROL OF CELLULAR DIFFERENTIATION

> **NIH NIH R01** · CORNELL UNIVERSITY · 1993 · $159,320

## Abstract

The proposed studies continue to investigate the regulation of cell
differentiation.  The emphasis is on early cell physiological responses
to inducers of terminal differentiation.  The potential regulatory role
of the RB (retinoblastoma) gene will be focused on.  The insight so
gained will hopefully promote the potential clinical use of
differentiation inducing agents to treat hematopoietic neoplastic
disease.  Chemotherapy of leukemia has historically relied on relatively
toxic agents to kill the tumor stem cells.  An alternative is to use
potentially less toxic agents to induce the terminal differentiation of
leukemia cells, thereby arresting their proliferative activity and
potentially restoring some of the differentiated cells that the patient
is otherwise deprived of.  To be able to optimally exploit this new
treatment modality, it becomes necessary to know how various agents act
at the cellular and molecular level to effect terminal differentiation of
neoplastic cells.  We will study this using a human leukemia cell line
which differentiates in vitro.  One target regulatory gene that has been
little studied in this regard is the tumor suppressor genes, of which the
RB retinoblastoma gene is the prototype.  Expression of this gene has an
apparent regulatory role in effecting terminal differentiation.  Thus it
becomes of interest to assessing tumor response and drug efficacy to
determine how RB is regulated during induced terminal differentiation and
how such agents affect its expression.  Molecular mechanisms of
differentiation induction therapy involving the RB tumor suppressor
gene's role in differentiation will thus be studied.  The working
hypothesis is that the RB gene has a regulatory role in effecting
terminal differentiation.  Our preliminary evidence indicates that RB
expression is down-regulated anteceding onset of terminal
differentiation.  Using a variety of agents to induce terminal
differentiation of HL-60 human promyelocytic leukemia cells as an in
vitro model, the role of the RB gene in effecting induced terminal
differentiation will be studied by characterizing regulation of its
expression and then experimentally manipulating that expression by
molecular biological techniques to determine the consequences on cellular
ability to differentiate. Because differentiation can be induced at will
in these cells, they provide a powerful tool for investigating this
process.

## Key facts

- **NIH application ID:** 3171358
- **Project number:** 5R01CA033505-12
- **Recipient organization:** CORNELL UNIVERSITY
- **SAM.gov UEI:** G56PUALJ3KT5
- **Principal Investigator:** ANDREW YEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $159,320
- **Award type:** 5
- **Project period:** 1983-08-01 → 1994-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171358

## Citation

> US National Institutes of Health, RePORTER application 3171358, CELL CYCLE SPECIFIC CONTROL OF CELLULAR DIFFERENTIATION (5R01CA033505-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171358. Licensed CC0.

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