This new atlas of leukemia proteomes may prove useful for medical laboratories and pathologists providing diagnostic and prognostic services to physicians treating leukemia patients
Researchers at the University of Texas at San Antonio (UTSA) and the University of Texas MD Anderson Cancer Center created the online atlases—categorized into adult and pediatric datasets—to “provide quantitative, molecular hallmarks of leukemia; a broadly applicable computational approach to quantifying heterogeneity and similarity in molecular data; and a guide to new therapeutic targets for leukemias,” according to the Leukemia Atlases website.
In building the Leukemia Proteome Atlases, the researchers identified and classified protein signatures that are present when patients are diagnosed with AML. Their goal is to improve survival rates and aid scientific research for this deadly disease, as well as develop personalized, effective precision medicine treatments for patients.
To perform the study, the scientists looked at the proteomic screens of 205
biopsies of patients with AML and analyzed the genetic, epigenetic, and
environmental diversity in the cancer cells. Their analysis “revealed 154 functional
patterns based on common molecular pathways, 11 constellations of correlated
functional patterns, and 13 signatures that stratify the outcomes of patients.”
Amina Qutub, PhD, Associate Professor at UTSA and one of the authors of the research, told UTSA Today, “Acute myelogenous leukemia presents as a cancer so heterogeneous that it is often described as not one, but a collection of diseases.”
“To decipher the clues found in proteins from blood and bone marrow of leukemia patients, we developed a new computer analysis—MetaGalaxy—that identifies molecular hallmarks of leukemia,” noted Amina Qutub, PhD (above), UTSA Professor of Biomedical Engineering and one of the UTSA study’s authors. “These hallmarks are analogous to the way constellations guide navigation of the stars: they provide a map to protein changes for leukemia,” she concluded. (Photo copyright: UTSA.)
To better understand the proteomic levels associated with AML, and share their work globally with other scientists, the researchers created the Leukemia Proteome Atlases web portal. The information is displayed in an interactive format and divided into adult and pediatric databases. The atlases provide quantitative, molecular hallmarks of AML and a guide to new therapeutic targets for the disease.
The NCI predicts there will be approximately 21,540 new
cases of AML diagnosed this year. They will account for about 1.2% of all new
cancer cases. The disease will be responsible for approximately 10,920 deaths in
2019, or 1.8% of all cancer deaths. In 2016, there were an estimated 61,048
people living with AML in the US.
“Our ‘hallmark’ predictions are being experimentally tested
through drug screens and can be ‘programmed’
into cells through synthetic manipulation of proteins,” Qutub continued. “A
next step to bring this work to the clinic and impact
patient care is testing whether these signatures lead to the aggressive growth
or resistance to chemotherapy observed in
leukemia patients.
“At the same time, to rapidly accelerate research in
leukemia and advance the hunt for treatments,
we provide the hallmarks in an online compendium [LeukemiaAtlas.org] where fellow
researchers and oncologists worldwide can build from the resource, tools, and
findings.”
By mapping AML patients from the proteins present in their
blood and bone marrow, the researchers hope that healthcare professionals will
be able to better categorize patients into risk groups and improve treatment
outcomes and survival rates for this aggressive form of cancer.
The Leukemia Proteome Atlases are another example of the
trend where researchers work together to compile data from patients and share
that information with other scientists and medical professionals. Hopefully, having
this type of data readily available in a searchable database will enable
researchers—as well as clinical laboratory scientists and pathologists—to gain
a better understanding of AML and benefit cancer patients through improved
diagnosis, treatment, and monitoring.
Scientists
at St. Jude’s have discovered that performing different genetic tests on pediatric
cancer patients, and then combining those test results, may help guide and
improve patient care.
The research was part of a St. Jude’s project called Genomes
for Kids (G4K), a study to determine how genetic information may be used to
diagnose and treat pediatric cancers.
Through this project, the researchers hope to learn why tumors form in
children and predict how tumors will respond to certain treatments.
‘It’s
a Whole Lot of Sequencing.’
Few tragedies are worse than cancer in children. This is where precision medicine treatments can be critical, and multiomics may play an important role in the development of new therapies.
Multiomics refers to a biological analysis approach in which
multiple “omes” are analyzed together in a collaborative way to locate relevant
biomarkers and functional relationships. These “omes” include:
To perform their research, the St. Jude scientists examined
253 pediatric cancer patients by conducting whole genome
sequencing (WGS), whole
exome sequencing (WES), and RNA
sequencing of their tumors. They also looked at the WGS and WES of
non-cancerous tissues extracted from the same cancer patients.
“It is a whole lot of sequencing. I admit that,” Scott Newman, PhD,
Group Lead, Bioinformatics Analysis at St. Jude’s, told The
Scientist.
“With results available in a clinically relevant time frame, and pricing becoming increasingly comparable to the radiology and pathology tests, WGS is becoming more accessible to pediatric oncology patients,” said Scott Newman, PhD (above), Group Lead, Bioinformatics Analysis, at St. Jude’s, in an American Society of Human Genetics (ASHG) news release. (Photo copyright: ASHG.)
As a result of their three-platform testing, the researchers
discovered there was at least one finding for each patient that could be useful
in providing a diagnosis, revealing risks for individual patients, or
pinpointing which drugs may be most beneficial for a particular patient in
nearly 200 (79%) of the cases. Such findings are at the heart of precision
medicine.
The researchers also compared their sequencing results to
cancer panels that use next-generation
sequencing (NGS) to target specific genes or mutations relevant to a
certain cancer phenotype.
During this portion of the research, they discovered that the cancer panels
missed 11% to 16% of actionable genes relating to diagnosis, prognosis, and
treatment.
“This is either good news or bad news, depending on how you
look at it,” Newman said. “Personally, I am amazed at how well these panels do
and how well they have been designed. But, if you want to know every mutation
that you would probably want to report, you have to do comprehensive
sequencing.”
First Multi-Platform Genomic Sequencing Study
“To
our knowledge, this is the first clinical study where this comprehensive three-platform
genomic sequencing approach was offered prospectively to all pediatric oncology
patients,” said Kim Nichols, MD,
Director, Division of Cancer Predisposition at St. Jude’s, in a St.
Jude’s blog post.
The testing costs $8,600 per patient, but is considered worth
it to improve patient diagnosis, prognosis, and treatment for pediatric cancer
patients.
“Compared with the cost of many
other procedures that children with cancer undergo, the cost is likely
comparable, or even less—for example, compared with complex surgical procedures
or multiple radiology tests,” Nichols said.
In addition, the test results are available in less than 30
days, which makes them more valuable, as time can be a critical asset to cancer
management.
The scientists hope this type of three-platform genetic
testing can help guide care for pediatric cancer patients.
“Because
so few of the molecular lesions in pediatric cancer are targetable by specific
drugs, currently it is the diagnostic and prognostic insights provided by the
three-platform approach that appear most clinically impactful,” said Nichols.
“From a diagnostic perspective, tumors may look the same under a microscope,
but the identification of specific genetic changes can direct you to the correct
diagnosis, and therefore, the most appropriate therapy. From a prognostic
perspective, you will have different risk stratifications depending on results.”
The results of the research were presented at the 2018
annual meeting of the American Society of Human Genetics in San Diego last
October. The St. Jude’s researchers hope that this type of research can drive
wider adoption of WGS in the assessment of pediatric tumors to improve patient
outcomes. Pathologists and medical laboratory scientists will want to watch for
additional research findings as the team at St. Jude’s uses this approach on
more pediatric cancer patients.
This research could lead to a useful liquid biopsy test that would be a powerful new tool for clinical laboratories and anatomic pathologists
Cancer researchers have long sought the Holy Grail of
diagnostics—a single biomarker that can quickly detect cancer from blood or
biopsied tissue. Now, researchers in Australia may have found that treasure. And
the preliminary diagnostic test they have developed reportedly can return
results in just 10 minutes with 90% accuracy.
In a news release, University of Queensland researchers discussed identifying a “simple signature” that was common to all forms of cancer, but which would stand out among healthy cells. This development will be of interest to both surgical pathologists and clinical laboratory managers. Many researchers looking for cancer markers in blood are using the term “liquid biopsies” to describe assays they hope to develop which would be less invasive than a tissue biopsy.
“This unique nano-scaled DNA signature appeared in every type of breast cancer we examined, and in other forms of cancer including prostate, colorectal, and lymphoma,” said Abu Sina, PhD, Postdoctoral Research Fellow at the Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), in the news release.
“We designed a simple test using gold nanoparticles that
instantly change color to determine if the three-dimensional nanostructures of cancer
DNA are present,’ said Matt
Trau, PhD, Professor of Chemistry at the University of Queensland, and
Deputy Director and Co-Founder of UQ’s AIBN, in the news release.
The team’s test is preliminary, and more research is needed before
it will be ready for Australia’s histopathology laboratories (anatomic
pathology labs in the US). Still, UQ’s research is the latest example of how
increased knowledge of DNA is making it possible for researchers to identify
new biomarkers for cancer and other diseases.
“We certainly don’t know yet whether it’s the holy grail for
all cancer diagnostics, but it looks really interesting as an incredibly simple
universal marker of cancer, and as an accessible and inexpensive technology
that doesn’t require complicated lab-based equipment like DNA sequencing,” Trau
added.
The UQ researchers published their study in the journal Nature Communications. In it, they noted that “Epigenetic reprogramming in cancer genomes creates a distinct methylation landscape encompassing clustered methylation at regulatory regions separated by large intergenic tracks of hypomethylated regions. This methylation landscape that we referred to as ‘Methylscape’ is displayed by most cancer types, thus may serve as a universal cancer biomarker.”
While methyl patterning is not new, the UQ researchers say they were the first to note the effects of methyl pattern in a particular solution—water. With the aid of transmission electron microscopy, the scientists saw DNA fragments in three-dimensional structures in the water. But they did not observe the signature in normal tissues in water.
“To date, most research has focused on the biological consequences of DNA Methylscape changes, whereas its impact on DNA physicochemical properties remains unexplored,” UQ scientists Matt Trau, PhD (left), Abu Sina, PhD (center), and Laura Carrascosa (right), wrote in their study. “We exploit these Methylscape differences to develop simple, highly sensitive, and selective electrochemical or colorimetric one-step assays for the detection of cancer.” (Photo copyright: University of Queensland.)
Their test averaged 90% accuracy during the testing of 200
human cancer samples. Furthermore, the researchers found the DNA structure to
be the same in breast, prostate, and bowel cancers, as well as lymphomas, noted
The Conversation.
“We find that DNA polymeric
behavior is strongly affected by differential patterning of methylcytosine
leading to fundamental differences in DNA solvation and DNA-gold affinity
between cancerous and normal genomes,” the researchers wrote in NatureCommunications.“We exploit
these methylscape differences to develop simple, highly sensitive, and
selective electrochemical or one-step assays for detection of cancer.”
Next Steps for the
“Gold Test”
“This approach represents an exciting step forward in
detecting tumor DNA in blood samples and opens up the possibility of a generalized
blood-based test to detect cancer, Ged Brady, PhD, Cancer Research UK
Manchester Institute, told The
Oxford Scientist. “Further clinical studies are required to evaluate
the full clinic potential of the method.”
Researchers said the next step is a larger clinical study to
explore just how fast cancer can be detected. They expressed interest in
finding different cancers in body fluids and at various stages. Another opportunity
they envision is to use the cancer assay with a mobile device.
DiCarlo told USA Today
that such a mobile test could be helpful to clinicians needing fast answers for
people in rural areas. However, he’s also concerned about false positives. “You
don’t expect all tumors to have the same methylation pattern because there’s so
many different ways that cancer can develop,” he told USA Today. “There
are some pieces that don’t exactly align logically.”
The UQ researchers have produced an intriguing study that differs
from other liquid biopsy papers covered by Dark Daily. While their test may need to be used in combination with other
diagnostic tests—MRI, mammography, etc.—it has the potential to one day be used
by clinical laboratories to quickly reveal diverse types of cancers.
For blood brothers Quest and LabCorp this is good news, since the two medical laboratory companies perform most of the testing for the biggest DTC genetic test developers
Should clinical laboratories be concerned about direct-to-consumer (DTC) genetic tests? Despite alerts from healthcare organizations about the accuracy of DTC genetic testing—as well as calls from privacy organizations to give DTC customers more control over the use of their genetic data—millions of people have already taken DTC tests to learn about their genetic ancestry. And millions more are expected to send samples of their saliva to commercial DTC companies in the near future.
This growing demand for at-home DTC tests does not appear to be subsiding. And since most of the genetic testing is completed by the two largest lab companies—Quest Diagnostics (NYSE:DGX) and Laboratory Corporation of America (NYSE:LH)—other medical laboratories have yet to find their niche in the DTC industry.
Another factor is the recent FDA authorization allowing DTC company 23andme to report the results of its pharmacogenetic (PGx) test directly to customers without requiring a doctor’s order. For these reasons, this trend looks to be gaining momentum and support from federal governing organizations.
Dark Daily has
reported on DTC genetic
testing for many years. According to MIT’s Technology Review, 26 million people—roughly
8% of the US population—have already taken at-home DNA tests. And that number
is expected to balloon to more than 100 million in the next 24 months!
“The genetic genie is out of the bottle. And it’s not going
back,” Technology Review reports.
The vast majority of the genetic information gathered goes into the databases of just four companies, with the top two—Ancestry and 23andMe—leading by a wide margin. The other two major players are FamilyTreeDNA and MyHeritage, however, Ancestry and 23andMe have heavily invested in online and television advertising, which is paying off.
In an op-ed response to a NYT editorial that warned readers to avoid 23andMe’s DTC genetic testing, 23andMe CEO and co-founder Anne Wojcicki (above) wrote, “We believe that consumers can learn about genetic information without the help of a medical professional, and we have the data to support that claim.” The FDA agreed and in February approved 23andMe to report pharmacogenetic test results directly to its customers. How this will play out for clinical laboratories remains to be seen. (Photo copyright: Inc.com.)
As more people add their data to a given database, the likelihood they will find connections within that database increases. This is called the Network Effect (aka, demand-side economies of scale) and social media platforms grow in a similar manner. Because Ancestry and 23andMe have massive databases, they have more information and can make more connections for their customers. This has made it increasingly difficult for other companies to compete.
Quest Diagnostics and LabCorp do the actual gene sequencing
for the top players in the DTC genetic testing sector. The expected wave of new
DTC genetic test costumers (74 million in the next 24 months) will certainly
have a beneficial revenue impact on those two lab companies.
Why the Explosion in Genetic
Testing by Consumers?
In 2013, just over 100,000 people took tests to have their
DNA analyzed, mostly using Ancestry’s test, as Dark Daily reported. By 2017, that
number had risen to around 12 million, and though Ancestry still had the
majority market share, 23andMe was clearly becoming a force in the industry,
noted Technology Review.
And now there are several health-related reasons as well. For
example, the study of pharmacogenetics has led clinicians to understand that
certain genes reveal how our bodies process some medications. The FDA’s clearance
allows 23andMe to directly inform customers about “genetic variants that may be
associated with a patient’s ability to metabolize some medications to help
inform discussions with a healthcare provider. The FDA is authorizing the test
to detect 33 variants for multiple genes,” the FDA’s press
release noted.
Controversy Over DTC
Genetic Tests
The use of DTC genetic tests for healthcare purposes is not without scrutiny by regulatory agencies. The FDA removed 23andMe’s original health test from the market in 2013. According to Technology Review, the FDA’s letter was “one of the angriest ever sent to a private company” and said “that the company’s gene predictions were inaccurate and dangerous for those who might not fully understand the results.”
23andMe continues to refine its DTC tests. However, the debate continues. In February of this year, the New York Times (NYT) editorial board published an op-ed warning consumers to be wary of health tests offered by 23andMe, saying the tests “look for only a handful of [genetic] errors that may or may not elevate your risk of developing the disease in question. And they don’t factor into their final analysis other information, like family history.”
Anne Wojcicki, CEO and co-founder of 23andMe, responded with her own op-ed to the NYT, titled, “23andMe Responds: Empowering Consumers.” In her letter, Wojcicki contends that people should be empowered to take control of their own health, and that 23andMe allows them to do just that. “While 23andMe is not a diagnostic test for individuals with a strong family history of disease, it is a powerful and accurate screening tool that allows people to learn about themselves and some for the most common clinically useful genetic conditions,” she wrote.
Nevertheless, privacy concerns remain:
Who owns the results, the company or the
consumer?
Who can access them?
What happens to them a year or five years after
the test is taken?
When they are sold or used, are consumers
informed?
Even as experts question the accuracy of DTC genetic testing
in a healthcare context, and privacy concerns continue to grow, more people
each year are ordering the tests. With predictions of 74 million more tests
expected in the next 24 months, it’s certain that the medical laboratories that
process those tests will benefit.
Customer relationship
management (CRM) plays a critical role in helping providers care for patients
with chronic diseases and clinical laboratories are part of those solutions
Home healthcare continues to boom in the US and more
technology companies each year—including Salesforce—strive to expand their
presence within the industry. This represents a significant shift in site of
service for a substantial and growing number of Americans. Equally true is that
home healthcare is an opportunity for clinical laboratories to serve this
increasing proportion of the American population.
Statistics tell the tale behind the boom in home healthcare.
The Centers
for Disease Control and Prevention (CDC) estimates that six in 10 adults in
the United States suffer from chronic diseases, such as cancer, and four in 10
adults live with two or more chronic illnesses.
This means that among medical laboratories and other
providers servicing the home healthcare industry demand for clinical laboratory
testing will increase.
Last year, approximately $103 billion was spent on home
healthcare services and that number is expected to reach $173 billion by 2026,
according to the Centers for Medicare and
Medicaid Services (CMS). Approximately 7.6 million people in the US now
require some level of in-home medical care. The overall employment of in-home
healthcare providers is projected to grow 41% between 2016 and 2026.
Efficient tools that assist home healthcare organizations and
their providers are critical. Customer
Relationship Management (CRM) platforms that combine data gathered during
office visits with patients’ living and economic situations are proving to be powerful
allies for treating chronic disease populations.
Social Determinants
of Health
One such CRM developer, Salesforce,
is rising to the demand by adding new features to its existing Health
Cloud platform. Originally introduced in 2016 as a way to improve how
healthcare and life sciences organizations connect with patients, this product
is one example of how Silicon Valley companies are attempting to make inroads
within the healthcare sector. Health Cloud’s newest functional upgrades include:
These social determinants of health are typically not
included in health records. But they can be vital information for healthcare
providers. Clinical laboratory managers should pay attention to “social
determinants of health” because this term describes a new dimension in medical
care and how patients with chronic diseases are managed.
“A lot of people in healthcare know about the importance of social determinants of health, but the volume of information is so great that being able to display things clearly and concisely in front of the [providers who] are using it—when they need it—makes it more operant and more prominent in the care of that patient,” Joshua Newman, MD, Chief Medical Officer at Salesforce, told MedCity News. (Photo copyright: San Francisco Business Times/Biz Journals.)
This is a critical factor. Healthcare providers who use Salesforce’s
Health Cloud can now record a patient’s social determinant information—such as,
transportation issues, housing status, and care network—directly into that
patient’s profile. Access to this type of information can give healthcare
professionals a more complete understanding of each patient’s unique situation.
Here are some examples from a Salesforce press
release that illustrate how social-determinants-of-health data can help
patients and care providers:
“A care provider that wants to limit a patient’s
risk for readmission can know if the patient has access to transportation or
the ability to purchase healthy meals.
“A life science organization that wants to help
patients adhere to their therapies, or properly use their medical devices, can
see a patient’s employment status and living arrangements, and thus offer the
necessary level of financial and in-home support.
“A payer organization can deliver personalized
preventative or wellness material to members based on the member’s education or
reading level.”
“Our industry continues to centralize and integrate patient
data, but it is critical that we stay focused on improving the patient
experience,” noted Ashwini
Zenooz, MD, in the press release. Zenooz is Salesforce’s Senior Vice
President and General Manager, Global Healthcare and Life Sciences. “By surfacing
critical factors of a patient’s life in a single view, we empower care
providers to personalize patient care experiences and improve outcomes.”
Many
existing CRM products cannot collect data from a variety of sources and then
sort and analyze that information to provide users with actionable
intelligence. Salesforce is attempting to fill that void among health and
medical software products with Health Cloud.
“Healthcare has been slower culturally, politically, and
socially to share their data. But what we’re seeing now is even those
organizations that have historically not shared their data are realizing they
can do a better job if they do,” Newman told MedCity News.
Outside Hospital Care
Increasing
Salesforce has also added a service it calls the Connected
Patient Journey to its Health Cloud platform. This service is an
integration between Health Cloud and Salesforce marketing, which can
personalize information given to patients based on their unique health needs.
Using this feature allows providers to build patient lists and use marketing techniques
to reach patients who would most benefit from specific campaigns and
information.
“The general overarching theme that unites all of these
innovations is that care is gravitating increasingly toward the home or outside
of the hospital and the doctor’s office,” said Newman.
Whether in-hospital or in-home, clinical laboratory tests play
a critical role in healthcare services. The ability for clinical laboratories
to enter patients’ test results data directly into CRM systems like Health
Cloud could help providers utilizing those systems better assist patients with
chronic diseases.
UPS’ program on
WakeMed Hospital’s Raleigh campus in N.C. is first drone delivery service
cleared by FAA for commercial purposes
UPS (NYSE:UPS) Chairman and CEO David Abney emphasizes patients, not packages, in the company’s new drive toward drone technology in medical laboratory specimen transport and logistics.
“Healthcare is a strategic imperative for us,” Abney said.
“We deliver a lot of important things, but lab [shipments] are critical, and
they’re very much a part of patient care.”
UPS entered the healthcare sector in 2000 with its acquisition of Livingston HealthCare. In 2016, the company acquired Marken, a move that Abney said, “sent a clear message to our customers that we were taking healthcare and clinical trials very seriously.”
UPS Chairman and CEO David Abney (above) explained the company’s new drive toward drone technology in medical laboratory specimen transport and logistics. Abney closed Day 1 sessions at the 24th Annual Executive War College on Lab and Pathology Management. (Photo copyright: DARK Daily.)
Clinical Laboratory
Specimens Delivered by Drone
With healthcare deliveries already a big part of UPS’ ground
business, the company now moves lab specimens by drone on WakeMed’s hospital campus in
Raleigh, N.C. The effort marks the first commercial daily drone service to be
cleared by the Federal Aviation Administration (FAA) for lab specimen
transport, and it is made possible through UPS’s new partnership with Menlo
Park, Calif.-based Matternet.
Matternet Founder and CEO Andreas Raptopoulos described how the new technology is impacting turnaround time, specimen stability, and viability. The “Future of Lab Logistics” session at EWC, featuring Raptopoulos and Shannon DeMar, Senior Marketing Manager Healthcare Strategy at UPS in Atlanta, Ga., brought questions about FAA regulations, risk mitigation, and more. Laboratory leaders are looking at how to take their logistics to the next level.
On-Demand/Same-Day
Delivery of Medical Lab Samples
The UPS/Matternet program represents a major milestone for
unmanned aviation in the United States, according to UPS, in a recent release.
Currently, the majority of medical samples and specimens are transported across
WakeMed’s expanding health system by courier cars. The addition of drone
transport provides an option for on-demand and same-day delivery, the ability
to avoid roadway delays, increase medical delivery efficiency, lower costs, and
improve the patient experience.
How drones, sensors, and new technologies are poised to
increase the quality and accuracy of specimen transport and logistics
represented just a slice of the first full day of sessions at Executive War
College. UPS is an official partner and sponsor.
Also speaking at the 24th Annual Executive War College on
Lab and Pathology Management:
Evolving market trends are creating both concern and
opportunities for the clinical laboratory industry. New sources of revenue are essential
at a time when fee-for-service prices for lab tests are decreasing.
Early registration is already open for 2020 Executive War College, happening April 28-29, in New Orleans.
