Know thy enemy.
It is as true for war as it is for cancer.
For today’s leukemia researcher, the enemy is the stubborn cancer cell that can survive chemotherapy, then regroup and attack the body again.
How do these cells outsmart the drugs that work so well on their compatriots?
Recently, a team of British researchers came up with a way to find out.
Using a highly sensitive microscope and a fluorescent dye, the team tracked the behavior of individual leukemia cells in the bone marrow of a living mouse.
It’s a technique called intravital microscopy, and it takes advantage of the mouse’s naturally paper-thin skull to take a peek inside living bone.
The scientists recorded the cells’ behavior under a variety of conditions, including before and after rounds of chemotherapy.
Like detectives examining surveillance footage, they then studied the videos to see where and when the cancer’s crimes unfolded.
What researchers discovered
What researchers found was a “massive, massive surprise,” Cristina Lo Celso, Ph.D., a professor at Imperial College London, and co-author of the paper, told Healthline.
She and her colleagues described their results in a paper published in the journal Nature earlier this month.
They expected the cells to proliferate from hotspots within the bone marrow, a popular hypothesis. Instead, the cells moved freely about the marrow without any apparent interest in hiding.
On top of that, “the harsher we made the chemotherapy, the faster the surviving leukemia cells ran around, almost like a hive of busy bees,” she wrote in a blog post.
In the group’s videos, the cancer cells (in red) can be seen wiggling and roaming the interior of the bone.
Lo Celso and her team designed the experiment with the intention of finding the cancer cells’ hiding places.
Scientists think that there are niches within the bone marrow that, for reasons not entirely understood, provide a safe haven for leukemia cells during chemotherapy.
These results suggest that scientists working on ways to blast cancer cells out of their hiding places are on the wrong track, Lo Celso says.
Instead, she wants to understand why the cells move around in response to treatment. It could be that cells that happen to move quickly are somehow less vulnerable to chemo drugs. Or that they metabolize the drugs faster. Or it could just be a coincidence.
What is important to test now, she says, is “whether the movement itself could be a new target that we could focus on.”
If all that movement is actually serving to help the cells shake off chemo, perhaps finding a way to slow the cells down is an avenue that researchers should explore.
Hesitations on the theory
But it’s too soon to discount the hiding hypothesis, Dr. Peter Aplan, a senior investigator with the National Cancer Institute, who wasn’t involved with the study, says.
He explains it this way: Lo Celso and her team looked at one specific type of leukemia known as T-cell acute lymphoblastic leukemia (T-ALL), a blood cancer that stems from malfunctioning white blood cells known as T cells and accounts for less than a quarter of all cases of ALL.
But T cells are different from other blood cells in a significant way. They originate in the thymus, a gland located just above the heart.
“They’re the blood cells that sort of breaks the rules,” Aplan told Healthline.
Other leukemias, like myeloid leukemia and B-cell lymphoblastic leukemia, originate from blood cells born in the bone marrow.
While T cells do wind up in the bone marrow, it’s not their home base. And that might mean they have a different relationship with the environment inside bone marrow than other blood cells do.
“It’s a bit of comparing apples to oranges,” Aplan said.
Those other types of leukemias may indeed have hideouts within the bone marrow, meaning that Lo Celso and her team haven’t necessarily upset the conventional way of thinking.
Path of destruction
But Aplan was intrigued by another finding the team reported.
Lo Celso’s researchers showed that as the cancerous cells invaded the bone marrow, they left a path of destruction in their wake.
“These cells don’t care much about where they are, they just keep moving and keep growing. But while they do so they actually ruin a lot of the environment,” Lo Celso said.
The cancer destroyed bone-making cells known as osteoblasts that are important for keeping the other blood cells healthy.
“We don’t quite know what are the mechanisms that lead to loss of healthy blood function, and being able to witness with our eyes how leukemia can be so destructive made us rethink how drugs might target the cancerous cells’ environment,” she said.
While current drug developments look for ways to blast cancer cells out of their cozy homes, perhaps a novel approach that seeks to preserve that environment and protect it from the cancer’s destructive influence might be fruitful.
But first, they need to understand how, exactly, the cells cause such destruction. And why chemotherapy incites such frantic behavior in leukemia cells.
“It’s the beginning of a story. We will be busy for the next few years,” Lo Celso said.