Toni Cable often speaks like a woman in a daze. Her thoughts come out in tangled tumbles, then tears appear on her cheeks.
But, as she does every day, she breathes deeply, tries again, and keeps going.
"It's hard," said Cable, 34, "but I have to."
Death and cancer have been a constant companion for not only Toni Cable but her extended Pike County family for six years. Her family — the Tackett/Cable branch of a large family tree — carries a rare gene mutation linked to the development of leukemia.
The mutation is so rare her family may be the only one in the world to pass it from generation to generation, said Dr. Ashish Kumar, an assistant professor in the Cancer and Blood Diseases Institute at Cincinnati Children's Hospital.
The latest wave of illness and death began when several of Toni Cable's uncles — Jimmy, Vanis and Elmer Tackett — were stricken with leukemia. The men were in their 40s and 50s when the disease took their lives.
Then Toni Cable's father, Homer Tackett, was diagnosed with leukemia. Two of her other uncles had been treated with bone marrow transplants that hadn't worked, so she thought her dad had little hope. Plus, because of the family history and financial strain, her dad was reluctant to seek treatment.
At the same time Homer Tackett's illness was progressing, the youngest of Toni Cable and her husband, Johnny Cable's two sons, Dalson Cable, 2, was having problems of his own.
The illness of the toddler and his grandfather were tied together through a series of medical inquiries, advanced genetic testing and not a small amount of luck by Kumar and others at the Cincinnati Children's Hospital.
The team is now trying to see how many of Toni Cable's cousins — Homer Tackett comes from a family of 11 children — may also carry the gene mutation.
Kumar said the revelation that the Tackett/Cable clan may be the only family in the world where this particular gene mutation is passed from generation to generation is filled with the potential of hope and tragedy.
Recognizing the presence of the gene mutation known as RUNX1 — as Kumar and his colleagues did this summer — could help the extended Tackett/Cable family in Pike County and beyond. And, Kumar said, being able to study how the leukemia takes root and responds to treatment offers a chance for an unprecedented medical look into the disease which could help others.
Hereditary RUNX1 is exceedingly rare, but the gene mutation is the most common anomaly tied to developing leukemia.
"There is a lot we don't know about this gene because there have not been good experimental subjects," said Kumar. "Here we have this entire family. We can study the biology of this gene and what it could be doing."
If a number of the extended family agree to be tested for the gene and take part in research, medical professionals can look at blood work before and after leukemia takes hold and develop better treatment for their family and others.
"There is a strong potential to learn some important things," said Kumar, who is treating Dalson Cable.
While the medical ramifications are great, Kumar never forgets that there is a family suffering at the heart of this case, he said.
"We have a family that is dealing with a big tragedy," he said. "The whole sequence of events was not pleasant and not what they wanted."
How it started
As Toni Cable explains how the events unfolded she seems, even months later, to find it hard to believe. Long before her uncles had become ill, some 16 years ago, she was told she had a condition called Idiopathic Thrombocytopenic Purpura. It causes low-blood platelets and bruising. The condition can usually be resolved with treatment and doesn't often present a serious health risk, Kumar said. And, in fact, Toni Cable didn't think much of it until Dalson was born and started having health problems. Doctors diagnosed him with Idiopathic Thrombocytopenic Purpura, too.
If she had minimal symptoms or symptoms she ignored, she couldn't brush off how it afflicted her baby. He suffered from painful inflammation of the joints. It caused severe rashes and skin infections and, most troubling to his mother, blisters on his eyes. Local family doctors referred the mother and child to Cincinnati.
Kumar knew immediately that Dalson Cable had been misdiagnosed, in part because Idiopathic Thrombocytopenic Purpura is not usually present at birth, nor does it usually cause such serious complications, he said.
He was intrigued by the family history because Toni Cable talked often about how sick her father was and his extended family's curse of leukemia.
Because of the family history, Kumar ordered genetic testing that was inconclusive. "We were stumped," he said.
This is where the luck comes in. As Toni Cable was seeking help for her son, a distant cousin was also trying to figure out what was wrong with her newborn. Kumar had ordered basic genetic testing on Dalson Cable that looked for sequences expected in DNA.
Genetic testing can be expensive, he said. What kind of testing can be done initially is often determined by what can be covered by insurance or the diagnostic capabilities of the lab where the test is deciphered. The Cables had no insurance.
The doctor treating the cousin ordered a more comprehensive genetic test that looked at not only sequences but also when sequences were repeated unexpectedly.
As it happens, both tests were to be reviewed by the same geneticist at Cincinnati Children's Hospital. That doctor recognized there might be a connection. Then he contacted Kumar who requested a more advanced exploration of the family's DNA — comparative genomic hybridization — which could examine things at a chromosomal level.
What was discovered is that in Dalson Cable's case, half of a gene had duplicated itself, leading to the RUNX1 mutation which has for years been linked to leukemia. Finding it in an extended family was extremely rare, he said.
So some of Toni Cable's family began to get test results. Toni Cable has been found to have the gene. Her mother, Emma Tackett, and older son, Dalton Cable, 15, don't.
Kumar began to interview other family members, beginning with the relatives of the three brothers who had died. The wife of one of the stricken brothers was a nurse who had kept many of his hospital records. Soon, a pattern was clear.
A family meeting
To help the family come to terms with the news, Kumar drove to the Cables' house in Virgie, 12 miles outside of Pikeville. There were so many cousins and kin waiting for him he had a hard time finding a place to park, he said. It was, "one of the scariest moments of my life," because "It is possible that each one of these people is looking at developing leukemia in each one of their lives," he said.
The family seemed resigned to learn as much as they could.
"They were ready with notebooks and pens and I basically held a class."
There was a sliver of good news. Because two brothers had died in spite of bone marrow transplants, the family assumed that the leukemia was somehow resistant to that treatment, Toni Cable said. But the bone marrow donors were relatives who also carried the mutated gene, making treatment ineffective. So, Kumar said, bone marrow transplants, the standard treatment for leukemia, may still be effective.
But that hope is little solace to Toni Cable and her family now. She cries when she talks of a cousin who died last year of leukemia at 36.
In her household of six, only two — her oldest son and mother — aren't sick or facing serious illness. Johnny Cable, Toni's husband, is unable to work as a truck driver because of an undiagnosed illness that doctors first thought might be spinal cancer.
Her father, Homer Tackett, continues to decline and is receiving Hospice care, which offers comfort but not a cure.
Just last spring Toni Cable and her mom ran two day care centers, employing several other people. But now her parents have moved in with her, taking up some of the space used for day care.
Money is more than tight. The family is on the verge of defaulting on its mortgage. Even paying for gas to get back and forth to hospital and doctor visits is a strain, she said. They recently just avoided getting their electricity cut off.
After months of unrelenting bad news, Toni Cable finds it more difficult to move forward, but she does hope some good comes out of her family woes with the help of Kumar. He recently added a full-time nurse coordinator to work on the case. He is hoping to get the word out to other distant Tackett relatives who have low-blood platelet issues or leukemia. He encourages family members to contact him but knows it's likely some would be hesitant to learn what could be bad news.
While he's eager to fill in the many branches of the wide Tackett family tree, for now helping Dalson Cable and his family is Kumar's main concern.
"We are trying to get the word out," he said, "but we want to give them the time they need."
Mary Meehan: (859) 231-3261. Twitter: @bgmoms. Blog: BluegrassMoms.com.