To Stop Blood Cancer, Target the Bone

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To stop acute myeloid leukemia, one of the deadliest blood cancers, targeting neighboring bone cells may be a better strategy than directly targeting the cells that give rise to the disease, suggests a new Columbia study.

The new study was published Jan. 19 in Cancer Discovery, a journal of the American Association for Cancer Research.

Acute myeloid leukemia (AML) is one of the hardest-to-treat blood cancers. And though it’s possible to achieve remission with drugs that target and destroy the stem cells that give rise to leukemia, the disease usually returns with deadly consequences. Patients relapse when new types of leukemic stem cells that elude all existing treatments surface.

Trying to develop additional drugs that target new stem cells is challenging, says cancer researcher Stavroula Kousteni, PhD, because the cancer will eventually mutate to circumvent the drugs.

Instead, Kousteni has looked for treatments that make the environment around the stem cells less hospitable for any type of leukemic stem cell. “We used to think blood cancers were driven exclusively by their own genetic mutations, but in recent years we’ve begun to realize that the cancer’s surroundings play an important role,” says Kousteni, professor of physiology & cellular biophysics and director of the Edward P. Evans Center for Myelodysplastic Syndromes (MDS) at Columbia University Vagelos College of Physicians and Surgeons.

Her new study shows that targeting neighboring cells in the bone marrow—osteoblasts, the cells which make bone—could turn a friendly environment for leukemia cells into a hostile one.

Targeting osteoblasts, cells that make bone, could turn a friendly environment for leukemia cells into a hostile one. Here, leukemia cells (red) are shown in the bone marrow (blue) of mice with acute myeloid leukemia. Photo courtesy of Stavroula Kousteni.

That’s because the osteoblasts are lured into helping leukemia stem cells, Kousteni’s team, led by Marta Galán-Díez, PhD, found. The new study reveals how leukemia cells lure the osteoblasts to function to their advantage by releasing a molecule called kynurenine. Kynurenine binds to a serotonin receptor (HTR1B) on the osteoblasts, sending the message to osteoblasts to help nurture leukemic cells by secreting an acute phase response protein (SAA1). SAA1 then tells the leukemia cells to make more kynurenine, and a vicious cycle ensues that leads to more disease progression.

The crosstalk between leukemia cells and osteoblasts can be broken, Galán-Díez and Kousteni found, suggesting a way forward for new AML treatments. In experiments with mice, they found that genetically eliminating the serotonin receptor that binds kynurenine blocks the progression of leukemic cells.

And in humanized mice carrying leukemia cells from patients and experiencing an AML relapse, an experimental drug that inhibits kynurenine synthesis “had a substantial effect in combination with traditional chemotherapy, slowing disease progression,” Galán-Díez says. (The drug, called epacadostat, is being tested in other cancers).

In the same study, Kousteni and Galán-Díez observed increasing levels of kynurenine and SAA1 in AML patients and in patients with myelodysplastic syndrome, another hematological cancer that often transforms to AML. Levels of both molecules increase with MDS progression to AML and SAA1 promotes proliferation of MDS and AML cells from patients, suggesting the same partnership between MDS or leukemia cells and osteoblasts is active in the human form of disease.

“The advantage of this approach is that it doesn’t matter which stem cells are causing the disease. They all need osteoblasts to grow, and if we can stop these two types of cells from communicating, we might be able to stop the disease,” Kousteni says.

In addition, the same approach may also prevent pre-leukemic conditions like MDS from progressing.

Wearable Remote Monitoring Device May Help Patients With Blood Cancers Identify When to Seek Follow-Up Care

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The use of a remote wearable device that monitors vital signs and physical activity was shown to be beneficial for patients with hematologic malignancies undergoing intensive treatment regimens, as it helped indicate when they needed to seek assistance from their health care provider, according to new research.

The study results, which were published in JCO Clinical Cancer Informatics, also showed that patients tolerated wearing the device.

Intensive treatment protocols for hematologic malignancies such as stem-cell transplantation, monoclonal antibody and CAR-T cell therapy may put patients at risk for things like infections, systemic immune reactions and arrhythmias (abnormal heartbeat). Additionally, patients may experience other medication side effects such as symptom exacerbation and cytokine release syndrome (which involves the cytokines overstimulating the immune system so that it attacks healthy organs).

“In fact, nearly every patient on these treatment protocols experiences at least one complication requiring follow-up treatment,” the authors wrote in the study.

While early diagnosis and treatment of these complications may reduce potential illness or death, treatment access is often affected by limited capacity at health care centers, increased costs and nursing staff shortages — which is why remote patient monitoring could be helpful in identifying and addressing complications early on.

To assess whether this was a feasible option for patients, the researchers observed 79 patients (54 in the inpatient setting and 25 outpatient), all of whom received a standard-of-care treatment for their cancer. The patients wore and self-managed a device that measured heart rate, oxygen levels and physical activity.

Most of the inpatient group (94.4%) and 64% of the outpatient group reported gastrointestinal symptoms (diarrhea, nausea and vomiting), pain, difficulty breathing or shivering during at least one visit from a health care provider. The vital signs and activity data were recorded by the devices for 1,304.8 days, accounting for 78% of potential recording time for the inpatient group and 84.6% for the outpatient group.

While the adherence to wearing the device was similar between groups, 35% of the inpatient group and 12% of the outpatient group dropped out of the trial, most commonly due to discomfort (27.2%). However, some dropped out due to having other medical procedures such as continuous blood pressure measurements, which made it stressful (22.7%). Some patients cited emotional stress (18.1%) or technical issues (13.6%) as reasons for dropping out.

“Despite the fact that patients on intensive treatment protocols for hematologic malignancies experience high symptom burden, our trial shows that they are willing and able to carry a wearable (device) for remote patient monitoring for a large proportion of the potential recording time and that most data gathered by a device will be interpretable,” the study authors wrote.

They added that the wearable band used in the trial was not a lifestyle device, meaning it did not have a display or fitness tracker. It was worn at the upper arm, and the study authors wrote that it was user-friendly, takes roughly 90 minutes to charge and has low interference with movements and therapy.

“To improve adherence, wearables should be even smaller and more convenient in terms of charging procedures,” the authors wrote.

To conclude, the researchers noted that this trial provides evidence that the wearable approach of consistent monitoring is possible and generally well-tolerated.

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Comedian Louie Anderson Hospitalized for Blood Cancer Treatment: Reports

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The Baskets star was diagnosed with diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma

Comedian Louie Anderson is undergoing treatments for blood cancer, according to multiple reports.

The Baskets star, 68, was diagnosed with diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma, and is currently getting treated at a Las Vegas hospital, his rep confirmed to Rolling Stone.

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“Iconic comedian Louie Anderson is currently in a Las Vegas hospital being treated for diffuse large B cell lymphoma, a form of cancer,” Glenn Schwartz, told the outlet in a statement. “He is resting comfortably.”

PEOPLE has reached out for further comment.

According to the Lymphoma Research Foundation, more than 18,000 people in the U.S. are diagnosed with diffuse large B-cell lymphoma (DLBCL) a year. And “despite being an aggressive lymphoma, DLBCL is considered potentially curable.”

Anderson has previously dealt with heart problems, and in 2003 underwent two procedures to correct an unspecified issue.

Last March, Anderson shared that he’s been working on losing weight, and has lost around 40 lbs. during the COVID-19 pandemic.

“I started the pandemic at about 370 or 380 pounds depending on what I was leaning on,” Anderson joked to host Conan O’Brien during an appearance on Conan on Tuesday. “And now I’m 340. I’m trying to get 275 so I can get into some of my mom’s actual clothes,” he added, referring to his female character on Baskets.

RELATED VIDEO: Louie Anderson ‘Knew It Was Right’ to Play a Woman on ‘Baskets’

Anderson said he’s been doing intermittent fasting, though he also poked fun at the weight loss strategy.

“I’m on the intermittent fast. One minute I’m eating, the next minute I’m not. Then I’m eating again. I figure, that way, I’m only eating for 30 minutes out of 60, which is half. I’m trying to get down to 40/20 so I’m not eating for 40 and eating for 20.”

Anderson first talked about losing weight for his health in 2018, when he opened up about growing up in a housing project as one of 11 children of an alcoholic father, and how he used food for protection.

Highly Contagious Blood Cancer Detected in Clams Threaten Marine Ecology

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HIMEJI, JAPAN - MAY 03: A basket of clams seen at Shinmaiko Beach on May 3, 2014 in Himeji, Japan. Clam digging is one of the popular leisure activities during the Golden Week, the holiday season from April 29 to May 6. (Photo : Photo by Buddhika Weerasinghe/Getty Images)

For humans, cancers are mostly hereditary and not contagious. However, the case may be different for clam species.

A very rare finding confirms that contagious blood cancer has spread among clam species in the Atlantic Ocean and the Mediterranean Sea, and human activity may have unintentionally contributed to the spread.

New research published in eLife reveals the “rare instance” of cancer contagion between clam species in the seas of Southern Europe. According to the study, such cases of leukaemia-like transmissible cancers have been observed in individuals from different species such as dogs and clams.

Researchers even suspect that a certain type of contagious cancer is also among the “greatest current threats” to Tasmanian devils.

“We set out to confirm whether a leukemia-like blood cancer found in some bivalves also infects Venus verrucosa, otherwise known as warty venus clams that are found in the seas of southern Europe,” study co-first author Daniel García-Souto, of the University of Santiago de Compostela (USC), Spain, said in the news release.

The type of transmissible cancers known as hemic neoplasias (HN) has been observed among clams in two regions in Spain.

A threat to the marine environment

Researchers tracked down the origin of the cancer and came up with an interesting finding. Among the 345 warty venus clams from coastal areas in Spain, Portugal, France, Croatia and Ireland, they were able to narrow down the search to two regions in Spain.

To their surprise, these two populations were actually 1,000 nautical miles away from each other, which suggests that human activity may have been involved, such as the shipping “from one region to another”.

The genomes of the tumors from both populations showed that the cancer cells originally developed in a species known as striped venus clams, and then jumped to warty venus clam.

“These findings confirm that contagious cancers can jump between clam species, which could be threat to the marine environment,” the researchers wrote. “The fact that the cancer was so similar in clams from the Atlantic coast and from the Mediterranean Sea, however, suggests that it may have emerged very recently, or that human activity helped it to spread from one place to another.”

Further analysis revealed that the cancer only affects warty venus clams.

Also read: Elusive Deep-Sea Creature Big Fin Squid Spotted 20,000 Feet Under the Sea

Preventing spread through human intervention

Study co-first author Alicia Bruzos, of the Francis Crick Institute in London said that it was possible that shipping activities have helped the cancer move from one place to another. According to the team, “if human activity is indeed a factor in the spread of the cancers, then it would also be possible to prevent its further spread through human intervention.”

“Our work confirms that contagious cancers can jump between marine clam species,” study senior author José Tubío, of USC, said in the news release. “As this may pose a potential threat to marine ecology, we need to keep studying and monitoring pathogens, including cancers, to help protect these species.”

Although there are still many unanswered questions about contagious cancers in bivalves, experts show broad interest in the clear findings and well-supported conclusion of the study.

Also read: Space Anemia: Space Travel Can Destroy 3 Million Red Blood Cells Per Second

Adult blood cancer-causing mutations occur in early childhood

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A new study, from the Wellcome Sanger Institute and the University of Cambridge, has traced these mutations to childhood, showing that they proliferate in the body over decades before cancer symptoms later in life.

The paper, published today (19 January 2022) in Nature, suggests that these mutations will cause blood cells to multiply at different rates in different people, and those in whom these mutations cause faster growth have cancer symptoms appearing earlier. If these mutations proliferate slowly, it is possible that the cancer symptoms would never appear, or be noticed after death by other causes.In the future, it might be possible to detect cancer warning signs earlier, potentially giving the opportunity to prevent or slow future cancer development.

Blood cancer is the fifth most common cancer in the UK and the third biggest cancer killer. More than 40,000 people are diagnosed with this disease every year, and about 15,000 of these people die from it1. There are over 100 different types of blood cancer, and the risk of blood cancer increases with age, with just under 40 per cent of people diagnosed being aged 75 or over1.

To better understand how blood cancer develops, scientists used whole genome sequencing technology of multiple blood cell clones from individual patients, along with in-depth genetic analysis of bone marrow and blood samples to establish the family history of individual blood cancers.

This allowed them to accurately estimate when the cancer causing mutations actually occurred during a patient’s lifetime. Scientists studied 10 people with myeloproliferative neoplasms − a type of cancer that causes stem cells in the bone marrow to produce too many blood cells. There are multiple mutations that are linked to the development of this type of blood cancer, however the most common cause of this cancer is a mutation called JAK2V617F.

The researchers, from the Wellcome Sanger Institute and the University of Cambridge, performed whole-genome sequencing on over 1000 clones derived from blood cell from the 10 patients diagnosed with Philadelphia-negative myeloproliferative neoplasms between the ages of 20 and 75. They then conducted targeted analysis of blood samples from the same individuals. This allowed them to both time the mutations that cause the cancer and track how fast the cancer grew in individuals over their lifetime.

The researchers were able to trace the ancestry of different blood cells and estimate the time at which each patient acquired JAK2V617F and other important mutations. They determined that, in these 10 patients, the first cancer-linked mutations emerged as early as a few weeks after conception and up to age 12, despite cancer symptoms presenting decades later in life.

From here, they estimated how long over a patient’s lifetime it took for these mutated cells to multiply to the point where cancer symptoms became visible.

These findings suggest that some blood cancers are more of a gradual, lifelong process in which a single cell acquires a cancer-linked mutation early in life and then slowly grows over decades, compared to a mutation that happened only a few years prior to diagnosis.

Research is now needed to understand if how this information could be used to help predict cancer risk in individuals who have these mutations. In addition to early detection, research is also needed into whether current treatments or new therapies could be used to slow or prevent the development of cancer once a person is identified as ‘at risk’.

Dr Nicholas Williams, first author from the Wellcome Sanger Institute, said: “By using whole genome sequencing and analysis of the pattern of sharing of mutations between blood cells, we were able to create family trees of these cells enabling us to identify when in life these shared mutations arose. This in-depth process has given us new insight into the development of blood cancer and will allow us to hopefully track the development of other blood cancers in the future.”

Professor Peter Campbell, senior author on the study from the Wellcome Sanger Institute, said: “JAK2V617F is an established cancer causing mutation for blood cancer, and for the first time our research has allowed us to trace when these mutations occurred in this specific type of blood cancer. Further research is now needed to see how this new information could help detect cancers sooner and if there are any existing or new therapies that could help treat the disease earlier.”

Dr Jyoti Nangalia, a senior author on the study from the Wellcome Sanger Institute and Wellcome-MRC Cambridge Stem Cell Institute, said: “Our research shows that cancer-driving mutations can occur in early childhood, even in the womb, to result in cancer diagnosis decades later. This is not something we were expecting. Blood cancer impacts thousands of lives every day and research such as ours into the timing and pace of how different cancers develop is crucial if we are going to find new ways to prevent these conditions. The success of our approach for tracking the origin and growth of this blood cancer could be applied to many other cancers and diseases.”

1. Facts and information about blood cancer. (2019). Blood Cancer UK. Available at https://bloodcancer.org.uk/news/blood-cancer-facts/ [accessed January 2022]

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