CD33 rs35112940: What Your Genotype Means for Gemtuzumab Ozogamicin
The rs35112940 variant is a specific change in the CD33 gene that has been studied for its potential influence on how leukemia cells respond to the drug gemtuzumab ozogamicin. Research suggests this variant may affect CD33 protein expression and the drug's efficacy in certain clinical settings.
What each genotype means
Enhanced gemtuzumab ozogamicin efficacy
Research indicates that individuals with this genotype may experience increased overall survival when treated with the leukemia drug gemtuzumab ozogamicin compared to those carrying the A allele. This variant is associated with CD33 protein expression levels, which can influence how effectively the drug targets leukemia cells. Please discuss these findings and your treatment plan with your oncologist or pharmacist.
This genotype is the major allele in many populations, though frequency varies significantly by ancestry.
Reduced gemtuzumab ozogamicin efficacy
Carrying one copy of the A allele is associated with reduced CD33 internalization and potentially lower efficacy of gemtuzumab ozogamicin compared to the GG genotype. This genetic difference may influence how your cells respond to this specific therapy. Please consult with your healthcare provider to understand how this information relates to your clinical care.
This heterozygous genotype is found in a significant portion of the population, consistent with a global minor allele frequency of approximately 0.1038 for the A allele.
Reduced gemtuzumab ozogamicin efficacy
Individuals with this genotype may have reduced CD33 internalization, which has been linked to lower efficacy of gemtuzumab ozogamicin in treating acute myeloid leukemia. This association suggests that the drug may be less effective at targeting leukemia cells in carriers of this genotype compared to those with the GG genotype. Always discuss medication choices and dosing with your clinical team.
This homozygous genotype is less common than the GG or AG genotypes, reflecting the lower frequency of the A allele in the general population.
Understanding the rs35112940 Variant
The rs35112940 variant is a single-nucleotide polymorphism (SNP) located within the CD33 gene. Specifically, it is a missense mutation, often referred to as Arg304Gly, where a guanine (G) is replaced by an adenine (A) at a specific position in the gene's sequence. This change occurs in exon five of the CD33 gene. Because it is a non-synonymous change, it results in an amino acid substitution in the resulting CD33 protein. Scientists study such variants to understand if they alter the structure or function of the protein, which in turn might influence how a patient's body interacts with targeted therapies. In the context of pharmacogenomics, this variant is one of several markers investigated to see if it can help predict how well a patient might respond to specific chemotherapy treatments.
The Role of the CD33 Gene
The CD33 gene provides instructions for making a protein that is primarily found on the surface of certain white blood cells, particularly those in the myeloid lineage. CD33 acts as a receptor and is often used as a target for specific cancer therapies, such as gemtuzumab ozogamicin (GO). Gemtuzumab ozogamicin is an antibody-drug conjugate designed to bind to the CD33 protein on the surface of leukemia cells. Once bound, the drug is internalized by the cell, where it releases a toxic agent to kill the cancer cell. Because the drug relies on the presence and proper function of the CD33 receptor to enter the cell, any genetic variation that changes how CD33 is expressed or internalized can theoretically impact the drug's ability to work effectively.
Research and Clinical Evidence
Research into rs35112940 has primarily focused on its association with clinical outcomes in pediatric patients with acute myeloid leukemia (AML) treated with gemtuzumab ozogamicin. Studies have observed that the variant allele (A) is associated with lower levels of CD33 protein on the surface of leukemic cells. Some clinical trials have reported that patients carrying the wild-type (GG) genotype experienced better survival rates or lower relapse risks compared to those with other genotypes when treated with GO. However, it is important to note that this evidence is considered limited and sometimes mixed; associations found in one study cohort were not always replicated in others. Furthermore, researchers have developed composite scores, such as the 'CD33_PGx6_Score,' which combine multiple SNPs to better predict drug response, indicating that rs35112940 is likely only one piece of a much larger, complex genetic puzzle.
What This Information Means for You
If you or a loved one are undergoing treatment for leukemia, it is natural to look for genetic information that might guide care. However, it is critical to understand that the clinical utility of the rs35112940 variant is still being researched and is not currently used as a standard diagnostic tool for making treatment decisions. The associations observed in scientific studies are statistical trends across large groups of people and cannot predict an individual's specific response to medication. Genetic factors are only one of many variables that influence how a patient responds to chemotherapy. You should never make changes to your medication or treatment plan based on genetic test results without consulting your oncologist or a clinical pharmacist. They are the only ones who can interpret these findings in the context of your overall health and specific clinical situation.
How common is this variant?
The global minor allele frequency for rs35112940 is approximately 0.1038, though frequencies can vary significantly across different ancestral populations.
Frequently asked questions
Is rs35112940 a diagnostic test for leukemia?
No, rs35112940 is not a diagnostic test for leukemia. It is a genetic variant studied in the field of pharmacogenomics to understand how genes might influence a patient's response to specific drugs.
Should I get tested for the rs35112940 variant?
Genetic testing for this variant is generally not part of standard clinical care. You should discuss the necessity of any genetic testing with your healthcare provider, who can determine if it is relevant to your specific treatment plan.
Does having the AA genotype mean the drug won't work?
Not necessarily. While some studies suggest an association between the AA genotype and reduced drug efficacy, these are statistical observations in groups. Individual responses to medication are complex and depend on many factors beyond a single genetic variant.
Where can I find more information about CD33 and drug response?
You can find reliable information through resources like the Pharmacogenomics Knowledge Base (PharmGKB) or by searching for peer-reviewed articles on PubMed. Always verify that the information comes from reputable medical or scientific institutions.
Sources & further reading
Educational information only, last refreshed 10/27/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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