Determining CHIP’s
Potential
Researchers have known about clonal hematopoiesis (clonal
expansion among hematopoietic stem cells [HSCs], resulting
in a population of genetically identical blood cells) for decades.
Clonal hematopoiesis is a hallmark of hematologic malignancy,
but can also be seen in healthy people. In the mid-1990s,
for instance, several groups reported a skewed pattern of
X-chromosome inactivation indicating clonal expansion in the
peripheral blood (PB) cells of older women. 1,2
But it was not until genetic sequencing advanced enough
to easily detect driver mutations associated with clonal hema-
topoiesis that researchers were able to define the prevalence
of clonal hematopoiesis in older people and better understand
its biological and clinical implications. Now clonal hemato-
poiesis is one of the most exciting topics in hematology – and
cardiovascular – research.
“Clonal hematopoiesis is a common age-related condition
in which a substantial fraction of the DNA in a person’s blood
is being generated by the clonal progeny of a single cell,” said
Steven McCarroll, PhD, Dorothy and Milton Flier Associate
Professor of Biomedical Science and Genetics at Harvard
Medical School. “That single cell underwent mutation that
caused the cell and its progeny to be able to proliferate relative
to other such cells.”
The cells that cause clonal hematopoiesis are typically
HSCs or progenitors committed to one of the blood-cell
lineages, he explained. Research has shown that the presence
of clonal hematopoiesis is associated with an increased
risk of hematologic malignancies, all-cause mortality, and
cardiovascular events; however, many people who have the
somatic mutations associated with clonal hematopoiesis
never go on to develop negative health events. 3-5
Given this finding, in 2015 researchers proposed the term
“clonal hematopoiesis of indeterminate potential,” or CHIP,
to describe people who have clonal hematopoiesis defined
by a mutation in a malignancy-associated gene, but without
evidence of disease. 6
As its name implies, the true potential of CHIP remains
undetermined, both for an individual patient diagnosed with
CHIP and for the overall affected population. Since CHIP was
defined, institutions such as the University of California San
Diego’s Moores Cancer Center and Memorial Sloan Kettering
Cancer Center, have established clinics that will focus solely on
this premalignant condition, including identifying patients at
the highest risk for developing a malignancy. Other institutions
such as the Dana-Farber Cancer Institute have created more
general “precursor state” clinics, both for those with CHIP
and for patients with analogous premalignant clonal states,
including monoclonal B-cell lymphocytosis and monoclonal
gammopathy of undetermined significance.
ASH Clinical News spoke with researchers and clinicians to
learn more about CHIP, the implications of a CHIP diagnosis,
and what it means for treatment decisions and follow-up.
May 2018
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