The unexpected link between leukaemia and vitamin B-6

Researchers have discovered a new leukemia treatment target after their study revealed vitamin B-6 is used by cancer cells. The development of a new medication is underway which could prove to be more successful than current treatments.

Researchers hope the manipulation of B6 dependence on leukemia will lead to better treatments.

Leukemia— a type of blood cancer that usually affects children and older adults — is the 10th most common cancer in the United States, accounting for 3.5% of all new cases of cancer in the world. L

The disorder is also the fifth highest cause of deaths from U.S. cancer, according to the National Cancer Institute. Figures show an estimated 22,840 people who died in 2019 from leukemia.

Second most common form of the disease is acute myeloid leukemia (AML). AML spreads quickly resulting in a comparatively low rate of survival. More than one-third of AML-patients live 5 years after diagnosis.

Cancerous cells in AML grow faster than they can be destroyed by current treatment. Finding a new drug that treats those cells differently is key to long-term survival.

Cancer cells use changes in metabolism— in which chemical reactions cause different cell functions to be turned on or accelerated — to grow and spread at an irregular rate.

As Lingbo Zhang, a fellow at Cold Spring Harbor Laboratory (CSHL), NY, explains in a video: “One central feature of[ a] leukemic cell is the reprogramming of its metabolic processes to sustain abnormal cell growth.”

A vitamin’s role

Zhang and a team from both CSHL and Memorial Sloan Kettering Cancer Center (MSK), NY, have now discovered how the division of AML cells happens so fast. Surprisingly it is about a particular vitamin.

Vitamin B-6 is essential to normal functioning of the body. It is derived primarily from a person’s diet and helps to develop cells and metabolism, as well as to generate neurotransmitters and red blood cells.

Taking genes from the cancerous white blood cells of AML, Zhang studied them in order to find more than 230 separate genes which were “very involved in leukemia.”

The team has tested each using CRISPR gene-editing technology to block each gene’s operation. The scientists have published their findings in the Celljournal of Cancer.

Used and abused by cancer

The researchers tried to find a gene that prevents cancer cells from spreading, and they did: a gene that produces a metabolic enzyme called pyridoxal kinase (PDXK).

PDXK controls the use of vitamin B-6 by making proteins which in turn produce the vitamin’s active form.

They don’t need vitamin B-6 all the time, because cells are healthy. When the time is right for cells to divide, the enzyme activates it.

Moreover, the researchers found that this vitamin was promoted by the enzyme in rapidly dividing cancerous cells.

This allowed the AML cells to proliferate, which could potentially lead to further growth and disease spread.

“We have shown this enzyme to be necessary for the growth of leukemic cells,” says Zhang, explaining: “Leukemic cells are addicted to vitamin B-6. You might call it a cancer weakness.”

Scott Lowe, MSK’s co-author and chair of the Cancer Biology and Genetics Program, adds: “We already knew that vitamin B-6 acted as a regulator for a whole series of enzymes needed to make the building blocks needed to grow and proliferate the cells.”

Yet, he says, “this work for the first time indicated that the pathway to vitamin B-6 might be critical for cancer sustainability.”

The way to more secure care

Most significantly, this combination of enzymes and vitamins could be a focus for a new, more successful form of therapy.

It would not be as easy as reducing consumption of vitamin B-6 from patients, as this can affect vital functions throughout the body, including the brain and the rest of the central nervous system.

Instead, Zhang and his colleagues collaborate with medicinal chemists to develop a drug that affects the enzyme PDXK.

In doing so, leukemic cells would be unable to take advantage of vitamin B-6.

Not only could the system slow or stop leukemia spread, but it could also avoid harming healthy cells that need vitaminB-6 to survive.

“We hope we can come up with a potential therapeutic strategy for this lethal disease,” Zhang said.

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