Breaking News
January 23, 2019 - Enemy number 1 – Air pollution and climate change top of WHO agenda
January 23, 2019 - Two Positive Phase III studies of Tafenoquine for the Radical Cure of Plasmodium vivax Malaria Published in The New England Journal of Medicine
January 23, 2019 - World Trade Center responders at increased risk for head and neck cancers
January 23, 2019 - Low-sugar diet leads to significant improvement in nonalcoholic fatty liver disease in boys
January 23, 2019 - Chaos in bodily regulation can optimize our immune system, finds study
January 23, 2019 - Short, text-based exercises can increase happiness for adults recovering from substance use disorders
January 23, 2019 - Body size may have greater influence on women’s lifespan than men
January 23, 2019 - Groundbreaking tool helps visualize neuronal activity with near-infrared light
January 23, 2019 - Scientists discover new genetic mutations causing inherited deaf-blindness
January 23, 2019 - UC team designs new naloxone-dispensing smart device
January 23, 2019 - Torrent Pharmaceuticals Limited Issues Voluntary Nationwide Recall of Losartan Potassium Tablets, USP and Losartan Potassium and Hydrochlorothiazide Tablets, USP
January 23, 2019 - Brain activity shows development of visual sensitivity in autism
January 23, 2019 - Two hour gap between dinner and sleep is overrated says Japanese research
January 23, 2019 - Fear and embarrassment are causing smear test numbers to plummet
January 23, 2019 - Protein-secreting device implanted in epileptic rats reduces seizures, improves cognition
January 23, 2019 - Reintroduction project recovers current wild population of green turtle in Cayman Islands
January 23, 2019 - Cancer survivors face greater financial burden related to medical bills
January 23, 2019 - PSA screening reduces prostate cancer deaths by 30%
January 23, 2019 - LSTM receives grant to help improve health of people living in informal settlements
January 23, 2019 - Hemochromatosis Mutation Linked to Other Morbidity
January 23, 2019 - Why early diagnosis of autism should lead to early intervention
January 23, 2019 - Aspirin May Lower Stroke Risk in Women with History of Preeclampsia
January 23, 2019 - Exposure to certain chemicals may be linked to decrease in blood pressure during pregnancy
January 23, 2019 - Bowel cancer on the rise among younger Australians
January 23, 2019 - Scientists have reversed memory loss in a mouse model of Alzheimer’s
January 23, 2019 - Defective molecular master switch could lead to age-related macular degeneration
January 23, 2019 - Researchers identify how concussions may contribute to seizures
January 23, 2019 - Short interval between last meal of the day and bedtime may not affect blood glucose levels
January 23, 2019 - Still Too Many Highway Deaths Tied to Speeding
January 23, 2019 - Prenatal valproate exposure linked to increased ADHD risk
January 23, 2019 - Compound identified that may help treat heart failure
January 23, 2019 - Undiagnosed Asthma in Urban Adolescents May Be Common
January 23, 2019 - Study describes metabolism of intestinal microbiota in babies for the first time
January 22, 2019 - Study links concussions to development of epilepsy
January 22, 2019 - Specialist-led hospital bereavement service may help restrain legal action after difficult deaths
January 22, 2019 - Genetic study reveals possible new routes to treating osteoarthritis
January 22, 2019 - Blood test may detect early signs of lung-transplant rejection
January 22, 2019 - Blood marker could aid in early prediction of Alzheimer’s progression
January 22, 2019 - Orthodontic treatment does not guarantee future dental health
January 22, 2019 - Rutgers researchers discover cause of bone loss in people with joint replacements
January 22, 2019 - Diversity among rural Africans extends to their gut microbiomes
January 22, 2019 - Newly developed biological system lets cells to create self-curving cornea
January 22, 2019 - VTv Therapeutics Announces Publication of Comprehensive Data in Science Translational Medicine Detailing the Discovery and Clinical Development of TTP399, including Results of Phase 2 AGATA Study
January 22, 2019 - about one in three adults with prediabetes has arthritis
January 22, 2019 - A look at how data is democratizing health care
January 22, 2019 - Alcohol-Linked Disease Overtakes Hep C As Top Reason For Liver Transplant
January 22, 2019 - Researchers identify new genes linked with age-related macular degeneration
January 22, 2019 - MPFI researchers identify synaptic logic for connections between two brain hemispheres
January 22, 2019 - New approach to reduce toxic protein production in ALS
January 22, 2019 - New study extends our knowledge of the link between miRNAs and cancer
January 22, 2019 - Asthma, eczema are not barriers to active lifestyle in teenagers
January 22, 2019 - Genetic changes may predict likelihood of relapse in breast cancer patients
January 22, 2019 - Antiepileptic drug use by people with Alzheimer’s disease linked to accumulation of hospital days
January 22, 2019 - IUPUI researcher receives $2.85 million grant to find ways to improve bone strength
January 22, 2019 - Precision medicine can help keep astronauts healthy during deep space missions
January 22, 2019 - Detecting signs of neurodegeneration earlier and more accurately
January 22, 2019 - Mouse studies challenge ‘inhibition’ theory of autism
January 22, 2019 - SSB launches BIOSTAT RM TX single-use bioreactor for producing consistent quality cellular products
January 22, 2019 - Experimental drug can positively modify key characteristic behavior in FXS patients
January 22, 2019 - Low-Income Women Lack Menstrual Hygiene Supplies
January 22, 2019 - Better mouse model built to enable precision-medicine research for Alzheimer’s
January 22, 2019 - Molecular profiling of precancerous lung lesions could lead to early detection and new treatments
January 22, 2019 - Genetic factors influence where fat is stored in our bodies
January 22, 2019 - The Psychology Behind Sticking to Your New Year’s Resolutions
January 22, 2019 - Scientists aim to find genetic causes of developmental abnormalities in the vagina and uterus
January 22, 2019 - New survey reveals scale of preventative healthcare challenge in the UK
January 22, 2019 - Looming Global Crisis Means People’s Diets Must Change: Experts
January 22, 2019 - Excessive social media use is comparable to drug addiction
January 22, 2019 - Researchers show how mechanical stress affects bone development
January 22, 2019 - Study takes a step closer to understanding the body’s response to opioid painkillers
January 22, 2019 - Unexpected connection found between feeding and memory centers of the brain
January 22, 2019 - A revolutionary approach transforms bone trauma treatment
January 22, 2019 - Early studies and recent clinical trials on nerve growth factor
January 22, 2019 - Dry Mouth and Older Adults: Information for Caregivers
January 22, 2019 - Are your grandparents getting tipsy at the holiday party?
January 22, 2019 - New machine learning algorithms identify early symptoms of urinary tract infections
January 22, 2019 - Young women skipping the Pap smear test due to embarrassment
January 22, 2019 - A global influenza pandemic high on the WHO’s agenda
January 22, 2019 - Amgen Makes All Repatha (evolocumab) Device Options Available In The US At A 60 Percent Reduced List Price
January 22, 2019 - Elastronics—hydrogel-based microelectronics for localized low-voltage neuromodulation
PPM1D gene confers a survival advantage to stem cells after chemotherapy

PPM1D gene confers a survival advantage to stem cells after chemotherapy

image_pdfDownload PDFimage_print

Chemotherapy has been associated with increased risk of leukemia years after the treatment, but what leads to that association is not clear. In this study published in the journal Cell Stem Cell, a team led by researchers at Baylor College of Medicine and MD Anderson Cancer Center combined clinical and laboratory studies to show that a gene called PPM1D, whose function in blood production was unknown, can confer blood cells exposed to the chemotherapy agent cisplatin a survival advantage that might favor the development of leukemia years later. The study suggests that the presence of this and other mutations should be considered when choosing chemotherapies.

The research team led by corresponding authors Dr. Margaret A. Goodell, director of the Stem Cells and Regenerative Medicine Center and professor of pediatrics at Baylor College of Medicine, and Dr. Koichi Takahashi, assistant professor in the department of leukemia at the University of Texas MD Anderson Cancer Center, initially found that PPM1D mutations turn up frequently in the blood of patients who get leukemia years after they first received chemotherapy for a previous disease. This finding sparked the question: how do PPM1D mutant cells become dominant when compared to their normal counterparts in the bone marrow? Do they ‘win’ because they are stronger and better at making more of themselves, or do they simply survive better in adverse conditions?

To address these questions, Goodell and Takahashi teamed up with Dr. Lawrence Donehower, professor of virology and microbiology at Baylor and co-author of the paper, who had been studying PPM1D for more than 20 years.

Survival in adversity

To understand what gives PPM1D mutants a competitive advantage, the researchers carried experiments in the lab mixing normal and PPM1D mutant cells together in a dish, growing them together and then exposing them to different environmental conditions. They were surprised to find that under normal conditions, PPM1D mutants and normal cells grew at the same rates. This suggests that the mutants are not intrinsically stronger. However, following exposure to cisplatin and some other chemotherapy drugs, the researchers observed that PPM1D mutants dramatically outcompeted normal cells.

“Taking the results all together, our findings suggest that chemotherapy acts as an evolutionary selection pressure that favors the survival of PPM1D mutant cells because they have better fitness than normal cells and ‘win’ under this specific type of stress,” said Joanne Hsu, a student in the Medical Scientist Training Program (MD/PhD) at Baylor and a member of the Goodell lab. “So, when a patient receives cisplatin-based chemotherapy, stem cells carrying PPM1D mutations survive better. This growth advantage could provide fertile ground for subsequent acquisition of mutations that eventually lead to the development of secondary leukemia years later. This study has been a translational journey from bedside observations to bench side.”

“I am most excited that the findings from clinical samples at MD Anderson generated a hypothesis that was verified in Dr. Goodell’s lab,” Takahashi said. “This study is a great representation of how combined forces between clinical and basic science investigators from the two institutions can disclose an important scientific discovery.”

The researchers’ findings in this study have multiple clinical implications for the future.

“Knowing that the selection of chemotherapeutic drugs can affect the risk of leukemia developing years later may assist physicians in the selection of specific treatments for their patients,” Goodell said.

Looking further ahead, this study also points towards PPM1D as a promising therapeutic target in patients with secondary leukemia.

“I am excited that this study shows that there is a need to develop therapeutic approaches to target overactive PPM1D signaling,” Donehower said.

Source:

https://www.bcm.edu/news/cancer/ppm1d-gene-gives-a-winning-boost-to-stem-cell

Tagged with:

About author

Related Articles