Scientists have discovered how blood cancer hijacks surprising sources of nutrients from its surroundings to promote its growth. New research published in nature shows that aggressive leukemia relies on taurine, a sulfur-containing amino acid commonly found in energy drinks, to shed from dedicated bone cells in its environment. This previously unknown cancer support mechanism may lead to novel therapeutic strategies for difficult-to-treat hematologic cancer.
The study, led by researchers at the University of Rochester, provides the first evidence that the taurine produced by bone marrow cells is a critical lifespan of leukemia stem cells, a rare cancer cell that promotes disease progression and resists routine treatments. By blocking this taurine supply line, scientists were able to significantly impair leukemia growth in laboratory models.
But how do amino acids become known as energy drink ingredients that are entangled in the development of cancer? What does this mean for patients with drug-resistant hematologic cancer?
Map the relationship between cancer and the environment
Hematologic cancers like acute myeloid leukemia (AML) grow in the bone marrow, where they interact with the various support cells that make up their microenvironment. The team used complex single-cell analysis techniques to map how these support cells change over time as leukemia progresses.
“While previous studies have described the cellular composition of normal bone marrow niches, their dynamic changes in the progression of leukemia remain uncertain,” the researchers explained in their study.
Their analysis showed that with the development of leukemia, the remodeling of the bone marrow environment was significantly remodeled, the mesenchymal stromal cells (MSCs) and immature osteocytes were significantly increased, and some vascular cells were reduced. These ever-changing cell populations produce different signals that can promote or inhibit the growth of cancer.
Taurine production and growth during cancer progression
One of the most important findings is that as leukemia progresses, bone marrow MSCs and developing osteocytes increase their taurine production. The researchers identified an enzyme called cysteine dioxygenase type 1 (CDO1), which is essential for taurine synthesis, which is highly expressed in these bone cells.
The team examined matched patients’ bone marrow samples and found an amazing pattern: CDO1 levels increased significantly when myelodysplastic syndrome (MDS) was converted to more aggressive AML and when AML recurred again after treatment.
These observations suggest that taurine may play a previously unknown role in the development of hematologic cancer. To test this hypothesis, the researchers conducted a series of revealed experiments:
- Taurine in leukemia bone marrow is 1.7 times that of normal bone marrow
- Prevents osteocytes from producing taurine in leukemia models to prolong survival by 13.5%
- Adding taurine to animal models accelerates disease progression, making it about three times more likely to die
- Blocking the uptake of taurine in leukemia cells greatly impairs its ability to establish and maintain disease
Leukemia depends on taurine transport
The researchers identified a protein called Tain (encoded by the SLC6A6 gene) that acts as a gate for taurine to enter leukemia cells. This protein is highly expressed in aggressive leukemia compared to normal hematostem cells.
When the researchers genetically removed tension from leukemia cells, they observed significant results. Animals receiving these modified leukemia cells survived significantly longer – in some experiments, 40% of the animals survived indefinitely. Leukemia cells without tension showed signs of impaired growth, increased cell death, and cell differentiation, rather than sustained stem-like growth.
Most importantly, removal of latt has minimal effect on normal hematostem cell function, suggesting a potential therapeutic window to target this process in patients.
Synergistic effects with existing treatments
The team found that SLC6A6 expression is particularly high in leukemia, which is resistant to Venetoclax, a drug increasingly used to treat AML. When they combined Venino Clarks with methods that block taurine uptake, they observed that synergistic effects significantly reduced leukemia cell growth.
Compared with the control group, primary human AML cells treated with GES, TAG or VENETOCLAX were reduced by 1.3 to 8.3 times, and greatly impaired the treated colony formation by 2.4 to 150 times. These data suggest that taurine inhibitors can bind to Venetoclax to block human Ammanm ammm ammm ammm ammm ammm ammm ammm ammm ammm ammm ammm ammm am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am am
How taurine promotes cancer growth
The researchers studied the molecular mechanisms and found that taurine activates MTOR, the main regulator of cell metabolism, and then drives glycolysis-process cells to generate energy from glucose. Without taurine, leukemia cells showed a sharp decrease in glycolysis and energy production.
This finding is particularly interesting because cancer cells are known to have abnormal metabolic needs. This study reveals that taurine is a previously unknown metabolic controller in leukemia stem cells.
They used metabolic tracers to confirm that taurine itself (not a derivative compound) is necessary for leukemia cells to maintain their aggressive growth patterns.
Impact on patients and treatment
The discovery that taurine supports leukemia growth has raised important issues in patient care. Taurine is found in many energy drinks and is sometimes used as a supplement to alleviate the side effects of chemotherapy.
“Since taurine is a common ingredient in energy drinks and is often provided as a supplement to alleviate the side effects of chemotherapy, our work shows that careful consideration of the benefits of taurine supplementation in leukemia patients may be of interest,” the researchers said.
While the study mainly uses genetic methods to block taurine uptake, the researchers also tested tight small molecule inhibitors in laboratory models. These compounds can impair leukemia cell growth and have minimal impact on normal blood stem cells, suggesting that pharmacological targeting of this pathway may be feasible.
As researchers continue to develop more effective taurine transport inhibitors, this newly discovered dependence could provide promising avenues for the treatment of aggressive leukemia and potentially be used in combination with existing therapies, such as venetoclax. For patients with drug-resistant hematologic cancer, these findings offer hope for new treatments not only targeting the cancer cells themselves, but also for the critical support they get from their surroundings.
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