# DETECTION OF DRUG RESISTANT CELLS IN ACUTE LEUKEMIA

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1988 · $193,514

## Abstract

The long term objective of this application is to develop methods
that enable the rapid identification of the mechanistic type and
frequency of antineoplastic drug resistant cells within populations
of blast cells obtained from patients with acute nonlymphocytic
leukemia (ANLL).  The importance of such methodologies cannot be
overstated, since they will not only aid in the immediate selection
of therapy, but will also give direction to future research in the
design of new therapeutic approaches, aimed at overcoming those
mechanisms of drug resistance identified.  These studies will focus
on the two most effective agents currently available for treatment
of ANLL, daunorubicin (DNR) and 1-B-D-arabinofuranosylcytosine
(ara-C).  We will utilize state-of-the-art flow cytometric and cell
sorting technology to enhance detection of drug resistant cells.
Our specific aims propose:  1) to perfect methods for detecting DNR
resistance by studying factors influencing the intracellular
biochemistry or pharmacology of DNR.  These studies will focus on
detection of markers of multidrug resistance such as P-glycoprotein
and intracellular DNR concentration, as well as other biochemical
parameters which may serve as markers for other forms of DNR
resistance; 2) to perfect methods for detecting ara-C resistance
by studying biochemical events related to ara-C metabolism and
mechanism of action.  To this end, we will attempt to produce a
monoclonal antibody that recognizes ara-C incorporated into DNA.
Nascent DNA containing ara-C, obtained by the pH-step alkaline
elution method, will be used as antigen.  We will also utilize the
pH-step alkaline elution method to study the effects of ara-C on
DNA synthesis; 3) to detect resistance to ara-C or DNR on the basis
of their cytotoxicity to leukemic cells.  These studies will
utilize a sensitive flow cytometric viability assay we have
developed that quantifies leukemic cell survival following exposure
to cytotoxic drug.

## Key facts

- **NIH application ID:** 3179812
- **Project number:** 2R01CA040188-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** DOUGLAS DONALD ROSS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $193,514
- **Award type:** 2
- **Project period:** 1985-07-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179812

## Citation

> US National Institutes of Health, RePORTER application 3179812, DETECTION OF DRUG RESISTANT CELLS IN ACUTE LEUKEMIA (2R01CA040188-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179812. Licensed CC0.

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