Recently, the MDS Foundation announced that two TP53 gene mutations result in worse patient outcomes in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). According to their international and multi center study, two mutated copies, as opposed to a single mutation, increase blood cancer severity. Ultimately, the MDS Foundation, a nonprofit designed to raise support and awareness for MDS, AML, and similar conditions, believes this knowledge will improve diagnosis and treatment options moving forward.
TP53 Mutations
When it comes to cancer, TP53 often plays a role. In fact, the gene is known as “guardian of the genome,” and is one of the most commonly mutated cancerous genes. A functional TP53 gene usually identifies damaged DNA. Next, it stops cells from passing on this damage. However, mutated TP53 genes are unable to protect cells from this damage. Previously, these mutations have been linked to shorter overall survival, disease recurrence, and disease severity. However, this is the first study that ever compared the results of having one gene mutation versus two.
Researchers analyzed data from 4,444 patients with myelodysplastic syndromes (MDS). Of these patients, around 33% only had one mutated TP53 gene. In comparison to patients with no TP53 mutations, the patients with only one mutation were similar. Both groups responded well to treatment, had low rates of disease progression, and survived longer. However, the other 66% of patients had two mutated TP53 genes. These patients experienced treatment-adverse MDS, fast disease progression, and quicker mortality. One researcher hypothesized that a single functional gene is enough to prevent against damage.
Moving forward, researchers believe that considering genomic data, and looking into MDS-related mutations, will help with utilizing the right – and most effective – treatment options.
Blood Cancer Subsets
Myelodysplastic Syndromes (MDS)
Myelodysplastic syndromes (MDS) are progressive conditions which prevent bone marrow from creating enough healthy blood cells. In patients with MDS, blood cells do not mature or leave the bone marrow. There are five types of MDS: refractory anemia, refractory anemia with sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Typically, MDS occurs after age 60. It affects males more than females. In around half of all cases, MDS progresses to acute myeloid leukemia (AML).
Many patients with MDS do not have symptoms. However, those who experience symptoms may have:
- Anemia
- Thrombocytopenia (low platelet count)
- Neutropenia (low white blood cell count)
- Fatigue
- Frequent infections
- Easy bruising and bleeding
- Pale skin
- Chest pain and shortness of breath
- Heart palpitations
Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a blood and bone marrow cancer. For those of you who don’t know, bone marrow is spongy tissue inside of your bones. It helps to make bone marrow. However, in AML, the bone marrow makes abnormal blood cells: myeloblasts (white blood cells), red blood cells, and platelets. AML occurs when the DNA of developing cells is damaged. As a result, the cells never mature and instead develop into immature, leukemic cells. These crowd out healthy blood cells, causing illness. Symptoms of AML include:
- Fever
- Fatigue
- Loss of appetite
- Bone pain
- Red spots on the skin
- Easy bruising and bleeding
- Frequent infections
- Pale skin
- Shortness of breath and/or difficulty breathing
