# REGULATION OF HUMAN MEGAKARYOCYTOPOIESIS

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 1988 · $72,586

## Abstract

Our goal is to acquire a more comprehensive understanding of the regulation
of human megakaryocytopoiesis.  Aspects to be addressed include:  (1)
determination of the role of macrophages (M) and thymic-derived lymphocytes
(T) in modulating megakaryocyte (Meg) development; (2) the effect of
isolated mature Meg on the in vitro growth characteristics of Meg
progenitor cells; and (3) the mechanism whereby megakaryocytopoiesis is
restored in post-cytoreductive cancer chemotherapy.  The core methodology
will rely on the cloning of human Meg colony forming units (CFU-M) in
culture. CFU-M-derived Meg colonies will be identified using an antibody
(Ab) probe that recognizes Megspecific glycoproteins and a second
fluorescein-labeled Ab directed against the probe Ab.  Our first aim will
be approached by deleting or adding M or T lymphocytes, or growth medium
conditioned by these cells, to cultures.  M will be isolated by adherence
to serum-coated petri dishes.  T lymphocytes and their helper/suppressor
subpopulations will be isolated by cell "panning" in petri dishes coated
with murine monoclonal antibody specific for the various lymphocyte
subpopulations.  Indirect methods for accomplishing this same purpose will
rely on complement-mediated cytotoxicity employing monoclonal antibodies
for deleting these cells from the Meg cultures.  The second aim will be
pursued utilizing a technique for isolating mature megakaryocytes based on
both density and velocity sedimentation.  Should an effect be demonstrated,
specific megakaryocyte components will be tested to see where the noted
effect lies.  Our third aim will be approached by serially studying
patients receiving such therapy.  The post therapy CFU-M population will be
assessed for cloning efficiency and proliferative capacity.  Cell suicide
techniques employing hydroxyurea and densitometry measurements for
quantitating cellular DNA will be carried out to assess DNA synthetic
activity and the development of ploidy in recovering megakaryocytes.
Production of CFU-M stimulatory factors in the patient's serum will be
serially monitored.  Primary platelet production problems or those that are
intragenically induced may cause serious therapeutic problems in patients
with cancer.  The anticipated studies may allow this problem to be
circumvented or at least alleviated by gathering basic information on human
megakaryocytopoiesis and the pertubations chemotherapy imposes on this
system.  (IS)

## Key facts

- **NIH application ID:** 3174512
- **Project number:** 5R01CA036896-05
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **SAM.gov UEI:** QD4MGHFDJKU1
- **Principal Investigator:** Alan M Gewirtz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $72,586
- **Award type:** 5
- **Project period:** 1984-03-01 → 1990-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174512

## Citation

> US National Institutes of Health, RePORTER application 3174512, REGULATION OF HUMAN MEGAKARYOCYTOPOIESIS (5R01CA036896-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174512. Licensed CC0.

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