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