CENTER FOR CANCER AND BLOOD DISORDERS
CENTER FOR CANCER AND BLOOD DISORDERS
FITTING THE GROOVE
“THESE KIDS CAN’T WAIT”
THE MOLECULE THAT FIGHTS INFANT LEUKEMIA
GETTING NEW PEDIATRIC CANCER DRUGS TO MARKET FASTER
Children’s Hospital Colorado
hematologist-oncologist Kathrin
Bernt, M.D., points to a cluster:
“These cells account for about
70 percent of infant leukemia.”
The root of the problem is
genetic: a gene called MLL gets
“translocated” to the wrong place
on the chromosome, preventing it
from performing the role it plays in
cell reproduction. As a stopgap, the
gene cooperates with an enzyme
called DOT1L to modify the protein
necessary to do its job, a process
known as methylation. The problem:
this configuration lacks the coding
to tell the cell to stop reproducing,
which creates a glut of immature
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The immune surveillance hypothesis holds that under normal
circumstances, the body’s own immune system recognizes mutated or
abnormal cells as nefarious agents and kills them off before a potentially
fatal infection — or cancer — starts.
Dr. Bernt proved it worked in mice
and dogs. Recently the drug made
the leap to people. “This is a class
of chemicals that’s never been
infused into humans before,”
Dr. Bernt says. “I was nervous
every day that something terrible
was going to happen.”
“The body’s own immune system,” says Children’s Hospital Colorado’s Lia
Gore, M.D., “is really most effective at fighting disease.”
Instead, the drug
eradicated leukemia
completely in some
patients, with next to
no side effects.
KATHRIN BERNT, M.D.
Magnified at 400x, immature
white blood cells dot the screen,
dark purple nuclei relieved here
and there by uneven haloes of
watery cytoplasm.
groove where SAM goes.” Deprived
of that essential element, the whole
process of rampant reproduction
that creates leukemic cells collapses.
cells that can’t fight infection,
in turn preventing normal blood
cells from forming, and clogging the
system. The leukemia survival rate
in infants — 50 percent, as opposed
to 80 to 90 percent in older kids —
is discouragingly low.
Children’s Colorado is using it to
treat patients right now. Still, it’s
not quite a miracle drug. In other
patients, the result was effectively
nil. The next step is to figure out
why, and if the drug can be modified
to be effective in more patients.
“But in order to
methylate you need a
methyl, a molecule
called SAM,” says
Dr. Bernt. “So
what if you make
a molecule similar
to SAM that won’t
methylate?”
It’s not often a physician
scientist gets to see the
results of her lab efforts
Myeloblast
translate so quickly to
patient care. The results
are literally visible:
Dr. Bernt queues up
another slide of white
blood cells developing.
These cells, treated with
the drug, are fully grown,
and will age and die, just as
cells should. “See this one with
the little pink flecks?” Dr. Bernt
points it out, visibly excited. “It’s
trying to become an eosinophil!”
Lymphoblast
Working with a
small pharmaceutical
company, which
engineered the individual
molecules, Dr. Bernt identified
a compound that worked: “It’s
chemically built to fit into the
In certain cases though, the immune system doesn’t recognize the
mutated cells of cancer as harmful, so it doesn’t fight them. That’s where
a new leukemia drug called blinatumomab comes in.
Initially developed by a small German pharmaceutical company,
blinatumomab acts as a molecular agent that binds healthy T cells to the
surface of the most common type of childhood leukemia cells. Essentially,
the drug helps the immune system kill leukemia by thrusting the malignant
cell right in the T cell’s face — a process Dr. Gore illustrates by thumbing her
nose: “It’s like, neener-neener-neener, come get me,” she says.
LIA GORE, M.D.
Or at least that’s the theory.
Whatever the reason behind its efficacy, &Ɩ