# MECHANISMS OF BIOLOGICAL PREVENTION OF LEUKEMOGENESIS

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 1988 · $270,879

## Abstract

Unique hematopoietic growth stimulatory factors have been identified in the
conditioned medium of a human bladder carcinoma cell line 5637.  One of
these, termed Pluripoietin, has been purified to homogeneity and is a
protein of Mr18,000 that stimulates human and murine CFU-GM (day 7), BFU-E
cfu-Mk., and CFU-GEMM.  In addition it induces differentiation of the
leukemic cell lines HL-60 and WEH1-3.A related pluripotent activity with
alpha CSF-like properties is also identified and is distinguished from the
former by ion-exchange chromatography and RP-HPLC.  Its action is species
restricted.  This molecule also will be purifed to homogeneity and both
pluripoietins (pCSF's) will be sequenced, cloned and used to raise
monoclonal antibodies.  Radioiodinated pCSF will be used for RIA
development and radioreceptor analysis on normal and leukemic cells.  In
vitro action of the pCSF's will be investigated under serum-free conditions
and in the absence of accessory cells that will be removed by a variety of
procedures including monoclonal antibody panning, FACS and
micromanipulation of single cells.  Synergism between the two pCSF's will
be investigated as will the requirement of a second factor such as
erythropoietin, thrombopoietin, GM-CSF, CSF-1, G-CSF and Eo.-CSF, for full
terminal differentiation of pluripotent stem cell targets.  Purification of
pluripotent stem cells will be undertaken using monoclonal antibodies in
normal or long term human marrow cell suspensions and in murine 5-FU
treated marrow and fetal yolk sac and liver.  Very early stem cells
(pre-CFU-GEMM, HPP-CFC) will be obtained by taking advantage of their lack
of certain cell surface antigens defined by monoclonal abs.(anti-la, L4F3),
their preferential localization in the adherent marrow, their dormant state
and 5-FU resistance.  Selective response of these cells to pCSF,
Interleukin-3,CSF-2 and other CSF species will be studied and attempts made
to develop continuous lines of normal or leukemic pluripotent stem cells.
The cell type in the marrow (macrophage, T-cell, preadipocyte, endothelial
cell) will be studied for factor production and biological role.

## Key facts

- **NIH application ID:** 3170419
- **Project number:** 5R01CA032516-06
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **SAM.gov UEI:** KUKXRCZ6NZC2
- **Principal Investigator:** MALCOLM A. MOORE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $270,879
- **Award type:** 5
- **Project period:** 1982-09-15 → 1989-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170419

## Citation

> US National Institutes of Health, RePORTER application 3170419, MECHANISMS OF BIOLOGICAL PREVENTION OF LEUKEMOGENESIS (5R01CA032516-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170419. Licensed CC0.

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