# LEUKEMIA INHIBITOR SUPPRESSES DIFFERENTIATION & IMMUNITY

> **NIH NIH R01** · NEW YORK MEDICAL COLLEGE · 1989 · $185,581

## Abstract

We have successfully induced leukemic cells from myelogenous leukemia
patienta and HL-60 promyelocyte-cell line to differentiate and mature to
macrophages in a liquid culture assay.  Conditioned culture medium (CM) of
PHA-activated normal T cells contains the maturation-inducing activity.
Analysis of total DNA content of single cells by flow cytometry
demonstrated clearly that differentiated macrophages possess the same
aneuploid DNA stemline as the undifferentiated patient cells, indicating
leukemic cells can differentiate independently of genetic abnormality.  The
developmental process revealed that CM first induced most of the leukemic
cells for one cell cycle division, then suppressed the DNA replication
preceding mature cell expression.  This process has also been delineated by
reduction of RNA content, development of adherent cells, morphology, and
acquisition of membrane receptors and functions.  We hope these analyses of
proliferation and maturation will represent a new and practical method to
study leukemia.  We are intending to study leukemic-patient cells with
simultaneous application of the methods probing proliferation and
differentiation defects.  This includes the investigation of a lack of
capacity to stop leukemic cells from replicating by comparing the
suppressive activity of CM of patients with normal proliferation of HL-60
cells.  Microassay technique to quantitate replicating cell number by
autoradiography will be used.  A possible excess or lack of proliferative
stimulation will be studied by cross-testing CM of patients and of normal
controls with patient and normal cells.  Similar methods will be used with
the culture assay to analyze whether there is a lack of CM
maturation-inducing activity for their own cells, thereby blocking their
differentiation.  The development of isolated immature cells of normal bone
marrow could be compared.  We also intend to identify the subset of T cells
producing the activities for cell proliferation, differentiation, and
suppression of proliferation.  Combining assays of proliferation and
differentiation on the same cells will enable us to understand the controls
of the leukemic cell growth.  (MI)

## Key facts

- **NIH application ID:** 3173551
- **Project number:** 5R01CA036040-06
- **Recipient organization:** NEW YORK MEDICAL COLLEGE
- **SAM.gov UEI:** WK63UJ11C2H7
- **Principal Investigator:** J. W. none CHIAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $185,581
- **Award type:** 5
- **Project period:** 1983-03-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173551

## Citation

> US National Institutes of Health, RePORTER application 3173551, LEUKEMIA INHIBITOR SUPPRESSES DIFFERENTIATION & IMMUNITY (5R01CA036040-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173551. Licensed CC0.

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