By Dr. Harriet Kamendi, PhD — Regulatory Toxicologist & CEO, Kandih BioScience

USA Today reports that cases of acute myeloid leukemia (AML) continue to rise, especially among adults over age 60 — and despite advances in targeted therapy, survival remains below 35% for many groups. (USA Today, 2025)

The public sees this as an oncology challenge.
Toxicologists see something deeper:

 AML is the intersection of environmental exposure, chemistry, genetics, and bone-marrow biology — making toxicology central to both prevention and safer therapy design.

If you work in biotech development, translational research, toxicology, or regulatory science, here’s the one clear idea:

Every breakthrough in leukemia treatment begins — and ends — with understanding how toxins affect the bone marrow.
What AML Teaches Toxicologists

AML is a malignancy where immature white blood cells accumulate in the bone marrow, preventing normal blood formation.
But its origins extend far beyond clinical presentation.

1. Environmental & Chemical Toxicology: Where AML Begins

For decades, toxicologists have connected AML risk to exposures such as:

Benzene

Formaldehyde

Petroleum solvents

Ionizing radiation

Even chronic low-dose exposure can damage hematopoietic stem cells — causing:

DNA strand breaks

Chromosomal translocations

Epigenetic dysregulation

Stem-cell exhaustion

Toxicologists quantify these risks, inform occupational exposure limits, and guide regulatory action.
This makes AML one of the clearest examples of chemical carcinogenesis still playing out in real time.

2. Therapeutic Toxicology: When the Cure Also Carries Risk

AML chemotherapy drugs — such as cytarabine, daunorubicin, or mitoxantrone — are powerful but toxic.

Common toxicological challenges include:

Cardiotoxicity (anthracyclines)

Neurotoxicity (high-dose cytarabine)

Hepatotoxicity

Severe myelosuppression

Modern product developers rely on regulatory toxicologists to:

Refine dosing regimens

Reduce systemic exposure

Improve selectivity

Avoid cumulative organ damage

This is where toxicology becomes the guardian of efficacy and survivability.

3. Regulatory Toxicology: The Safety Backbone of AML Drug Development

Before any AML therapy reaches first-in-human trials, the FDA requires extensive nonclinical safety testing under ICH S9 guidelines, including:

Genotoxicity

Reproductive toxicity

Toxicokinetics

Off-target tissue toxicity

Dose-range finding studies

Regulatory toxicologists ensure these data tell a consistent safety narrative — preventing clinical holds, protocol amendments, or post-market safety surprises.

Done correctly, toxicology shortens timelines by preventing derailments.

 Tactical Lessons for Developers & Translational Teams

 Design Early for Selectivity

Start by ensuring your molecule targets leukemia cells rather than the bone marrow niche.

Use:

Human bone-marrow organoids

CRISPR-edited AML cell lines

Predictive off-target toxicity models

These systems catch safety red flags months before animal studies.

 Leverage Mechanistic Toxicology Data

Mechanistic insights — such as benzene’s creation of DNA adducts or ROS-driven stem-cell injury — can inspire novel AML therapies with lower long-term toxicity.

This is where toxicology and drug design can truly co-innovate.

 Regulatory Alignment from Day One

Plan your preclinical strategy around FDA and EMA expectations:

21 CFR Part 312

ICH S9

FDA Oncology Center of Excellence frameworks

Early alignment = fewer repeat studies + faster IND approvals.

 Model Human Variability Upfront

AML disproportionately affects older adults — a population with:

Reduced detoxification capacity

More comorbid exposures (smoking, solvents, medications)

Altered pharmacokinetics

Population PK modeling helps define safe dose ranges and improves clinical trial inclusion criteria.

 My Opinion: The Blind Spot in Cancer Innovation

As a regulatory toxicologist, my view is simple:

Modern oncology overestimates molecular targeting and underestimates exposure science.

AML does not exist in a vacuum.
Patients come with decades of chemical exposures that shaped their disease and will shape their treatment response.

If a leukemia originates from chemical insult, our therapies should be informed by the same toxicological mechanisms that drove it.

Drug development and toxicology cannot be separated — not in AML.

 Toxicology isn’t the caboose of cancer innovation. It’s the engine of safe progress.

 The Bottom Line

AML and toxicology share a molecular blueprint: both seek to understand how small exposures cause big biological consequences.

For developers, the lesson is clear:

The next generation of safer AML therapies will come from teams where toxicologists, pharmacologists, and regulators collaborate from day one — not at the finish line.

This is how we design therapies that kill cancer without compounding toxicity.

 References

1. USA Today. Acute Myeloid Leukemia: What is it? https://www.usatoday.com/story/life/health-wellness/2025/11/24/tatianna-schlossberg-acute-myeloid-leukemia/87445422007

2. FDA. Nonclinical Evaluation of Anticancer Pharmaceuticals (ICH S9). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/s9-nonclinical-evaluation-anticancer-pharmaceuticals

3. Science Direct. Occupational Benzene Exposure and Blood Cancers. https://www.sciencedirect.com/science/article/pii/S1877782125000396

4. Snyder R. Benzene and Leukemia: Toxicology, Mechanisms, and Risk Assessment. Crit Rev Toxicol. 2002. https://pubmed.ncbi.nlm.nih.gov/12071572

5. Estey E, Döhner H. Acute Myeloid Leukemia. Lancet. 2023. https://pubmed.ncbi.nlm.nih.gov/17126723