PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

HOXA9 tracking reveals RBM5 dual function and therapeutic potential for acute myeloid leukemia

HOXA9 tracking reveals RBM5 dual function and therapeutic potential for acute myeloid leukemia
2024-01-12
(Press-News.org) (Memphis, Tenn – January 12th, 2024) The protein HOXA9 is overexpressed in most acute myeloid leukemia (AML) cases and is associated with poor patient outcomes. However, HOXA9 is a difficult protein to target therapeutically, so researchers at St. Jude Children’s Research Hospital looked for ways to extinguish it indirectly. Using CRISPR/Cas9 screening, the researchers identified RBM5, demonstrating a causative link between RBM5 expression and leukemia cell proliferation. This link is driven by a novel dual function of RBM5 as both a DNA and RNA handler in gene expression. The research was published today in Genome Biology. 

 

Overexpression of the protein HOXA9 is a hallmark of AML, present in over 70% of cases, often with poor prognosis. While this would implicate it as a useful drug target, the protein’s role as a transcription factor has left it “undruggable” because a drug that interferes with HOXA9 would likely have numerous other off-target effects. This inspired researchers to approach the problem from a different angle by investigating the proteins HOXA9 works alongside and relies on to function. Chunliang Li, PhD, St. Jude Department of Tumor Cell Biology, co-corresponding author on this paper, is one such researcher. Through his recent work devising an unbiased CRISPR screening strategy to identify targets of HOXA9, he uncovered a network of opportunities. 

 

“This has been a continued effort since my lab was established in 2017,” said Li, “We built up this unique reporter system in early 2019, which is the first reporter authentically representing HOXA9 expression in these leukemia systems.”  

 

The CRISPR/Cas9 screening approach is elegantly simple in design but incredibly effective. It involves attaching a fluorescent tag to the HOXA9 gene and inserting it into leukemia cell lines. This enables researchers to track differences in expression levels by looking at fluorescence in cells.  

 

“We wanted to identify a more targetable or novel regulator. So, we conducted an unbiased whole genome CRISPR screening to target all the genes expressed in cells,” Li stated. This allowed the researchers to examine different pathways where HOXA9 left its fluorescent fingerprint. 

 

To the researchers’ surprise, splicing factors appeared to be the most represented pathway.  

“This was quite surprising to us because splicing factors regulate different combinations of the transcript, but not usually the level. Our data suggested these proteins control the HOXA9 expression level,” said Li. “So, we hypothesized maybe the splicing factors have another function, like a dual function.” 

 

The protein that stood out was the RNA-binding protein RBM5. The researchers found that RBM5 is highly expressed in leukemia cells as opposed to other cell types and that both the DNA- and RNA-binding sites are vital to its oncogenic functions. While the RBM family comprises vital RNA splicing factors, their function in DNA transcription was unknown. To address the direct transcriptional regulation of RBM5/HOXA9, the researchers generated a system to allow the acute degradation of RBM5.  

 

“Immediately after RBM5 protein was removed from cells, HOXA9 mRNA levels were significantly reduced,” Li explained, “This reduction happened as early as two hours later but did not impact splicing events of HOXA9.” Additionally, leukemia cells stripped of their ability to produce RBM5 were rescued through overexpression of HOXA9, further demonstrating the link between the two proteins.  

 

These results have Li looking to explore the protein as a drug target to treat AML.  

 

“We think RBM5 is a very good dependency gene, which should be a good target based on our functional assays,” he said. “If we can specifically target the DNA binding affinity of these proteins, we should be able to combine with other existing therapies in synergy to target HOXA9-driven leukemia.” 

 

Authors and funding 

The study’s first author is Mengli Zhang, Soochow University. The co-corresponding author is Peng Xu, Soochow University. Other authors include Judith Hyle, Shaela Wright, Zhenling Liu, Wojciech Rosikiewicz, Beisi Xu and Liusheng He of St. Jude; Xiaowen Chen of Shenzhen Children’s Hospital; Ye Xin, Yingcai Jin, Jianxiang Zhang, Xue Yang and Xinfeng Chen of Soochow University; Hong Liu, Nana Ping and Depei Wu of The First Affiliated Hospital of Soochow University; and Feiqiu Wen of Shenzhen Children’s Hospital. 

 

The study was initially supported by grants from ALSAC, the fundraising and awareness organization of St. Jude. 

 

St. Jude Media Relations Contacts 

Chelsea Bryant  
Desk: (901) 595-0564 
Cell: (256) 244-2048 
chelsea.bryant@stjude.org 
media@stjude.org 

 

Rae Lyn Hartley  
Desk: (901) 595-4419 
Cell: (901) 686-2597 

raelyn.hartley@stjude.org 

media@stjude.org 

END

[Attachments] See images for this press release:
HOXA9 tracking reveals RBM5 dual function and therapeutic potential for acute myeloid leukemia

ELSE PRESS RELEASES FROM THIS DATE:

Male gender expression in schools is associated with substance abuse later in life

2024-01-12
A new study led by researchers at the University of Chicago found that changes in male gender expression from adolescence to young adulthood align closely with the gender norms present in individuals’ school environments, and that these trajectories are associated with subsequent patterns of substance abuse. Amidst a growing consensus among social science researchers that separates gender from biological sex, gender has come to be defined as a constellation of expected behaviors, attributes, preferences and beliefs typically associated with a specific gender identity. Prior research shows that traditional models of male gender identity, constructed over time through sociocultural ...

Goldstein selected to help lead statewide task force addressing heart disease and stroke

Goldstein selected to help lead statewide task force addressing heart disease and stroke
2024-01-12
LEXINGTON, Ky. (Jan. 12, 2024) — Larry Goldstein, M.D., chair of the University of Kentucky Department of Neurology, has been selected to serve as co-chair of The Kentucky Heart Disease and Stroke Prevention (KHDSP) Task Force representing stroke systems of care across the state.  Goldstein is co-director of the Kentucky Neuroscience Institute, co-director of the UK Neuroscience Research Priority Area, contact PI for the state’s CDC Coverdell National Acute Stroke Program grant, and interim director of the UK-Norton Healthcare Stroke Care Network. Additionally, he also sits on ...

Healthy Hearts for Women event marks 10 years of raising awareness

Healthy Hearts for Women event marks 10 years of raising awareness
2024-01-12
LEXINGTON, Ky. (Jan. 12, 2024) — The University of Kentucky will mark a decade of raising awareness and continuing its effort to warn women about the dangers of heart disease with the annual Healthy Hearts for Women Symposium. Cardiovascular disease is the No. 1 killer of women, causing 1 in 3 deaths each year, according to the American Heart Association. Yet, only 44% of women recognize that cardiovascular disease is their greatest health threat. “We see the evidence of this devastating statistic right here in Kentucky. The Commonwealth has the highest rates of deaths due to cardiovascular disease in women ...

Building trust and saving lives: A community approach to genetic education

Building trust and saving lives: A community approach to genetic education
2024-01-12
Changes to DNA, known as mutations, can increase the likelihood of developing cancer. Specifically, people with mutations in their BRCA 1 and 2 genes are substantially more likely to develop hereditary breast and ovarian cancers. But how do people know if they have these mutations? Genetic testing. Genetic testing allows doctors to see these microscopic changes. Knowing these mutations exist, doctors will check for signs of breast and ovarian cancers more often. Yet minorities, especially Black women, are less likely to participate in genetic testing. ...

Using idle trucks to power the grid with clean energy

2024-01-12
University of Waterloo researchers are tapping into idled electric vehicles to act as mobile generators and help power overworked and aging electricity grids. After analyzing energy demand on Alberta’s power grid during rush hour, the research proposes an innovative way to replenish electrical grids with power generated from fuel cells in trucks. “Canada’s power grids need to be upgraded,” said Dr. XiaoYu Wu, lead researcher and a professor in Waterloo’s Department of Mechanical and Mechatronics Engineering.  “But the price ...

Activity of pazopanib in EWSR1-NFATC2 translocation-associated bone sarcoma

Activity of pazopanib in EWSR1-NFATC2 translocation-associated bone sarcoma
2024-01-12
“Pazopanib is a multi-kinase inhibitor that is currently approved for treatment of advanced renal cell carcinoma and chemotherapy-refractory soft tissue sarcoma.” BUFFALO, NY- January 12, 2024 – A new case report was published in Oncoscience (Volume 10) on September 20, 2023, entitled, “Activity of pazopanib in EWSR1-NFATC2 translocation-associated bone sarcoma.” Pazopanib, a multi-kinase VEGF inhibitor, is currently FDA approved for advanced renal cell carcinoma and advanced soft tissue sarcoma; but limited evidence exists on its efficacy in bone sarcomas. In this case report, researchers Mohamed A. Gouda, ...

3D in vitro human atherosclerosis model for high-throughput drug screening

3D in vitro human atherosclerosis model for high-throughput drug screening
2024-01-12
BIRMINGHAM, Ala. – A groundbreaking 3D, three-layer nanomatrix vascular sheet that possesses multiple features of atherosclerosis has been applied for developing a high-throughput functional assay of drug candidates to treat this disease, University of Alabama at Birmingham researchers report in the journal Biomaterials. “Current in vitro atherosclerosis models have significant limitations, including the lack of three-layer vascular architecture and limited atherosclerotic features,” said Ho-Wook Jun, Ph.D., a professor ...

The early bird (or scientist) gets the worm

The early bird (or scientist) gets the worm
2024-01-12
RIVERSIDE, Calif. -- Size does not matter. Certainly not when it comes to tiny worms securing the attention of biologists. One such biologist, Morris F. Maduro at the University of California, Riverside, has just been awarded a grant of nearly $1.3 million from the National Science Foundation, or NSF, to study a worm (or nematode) about a millimeter in length. The research project will focus on the gut of Pristionchus pacificus. Like most nematodes, P. pacificus develops quickly, its growth from embryo to adult taking just four days. It is a complete ...

News media trigger conflict for romantic couples with differing political views

News media trigger conflict for romantic couples with differing political views
2024-01-12
CHAMPAIGN, Ill. — By one estimate, as many as 30% of people in the U.S. are in romantic relationships with partners who do not share their political views. In today’s hyperpartisan climate, where Democrats and Republicans have difficulty talking to each other and their views are polarized about media outlets’ credibility, how do couples with differing political perspectives decide which media to follow? And how do these decisions affect their discussions on political issues and their relationship ...

Earth-sized planet discovered in ‘our solar backyard’

Earth-sized planet discovered in ‘our solar backyard’
2024-01-12
MADISON — A team of astronomers have discovered a planet closer and younger than any other Earth-sized world yet identified. It’s a remarkably hot world whose proximity to our own planet and to a star like our sun mark it as a unique opportunity to study how planets evolve. The new planet was described in a new study published this week by The Astronomical Journal. Melinda Soares-Furtado, a NASA Hubble Fellow at the University of Wisconsin–Madison who will begin work as an astronomy professor at the university in the fall, and recent UW–Madison graduate Benjamin Capistrant, now a graduate student at the University of Florida, co-led the study with co-authors from ...

LAST 30 PRESS RELEASES:

Youngest in class at higher risk of mental health problems

American Heart Association announces new volunteer leaders for 2025-26

Gut microbiota analysis can help catch gestational diabetes

FAU’s Paulina DeVito awarded prestigious NSF Graduate Research Fellowship

Champions for change – Paid time off initiative just made clinical trials participation easier

Fentanyl detection through packaging

Prof. Eran Meshorer elected to EMBO for pioneering work in epigenetics

New 3D glacier visualizations provide insights into a hotter Earth

Creativity across disciplines

Consequences of low Antarctic sea ice

Hear here: How loudness and acoustic cues help us judge where a speaker is facing

A unique method of rare-earth recycling can strengthen the raw material independence of Europe and America

Epilepsy self-management program shows promise to control seizures, improve mood and quality of life

Fat may play an important role in brain metabolism

New study finds no lasting impact of pandemic pet ownership on human well-being

New insights on genetic damage of some chemotherapies could guide future treatments with less harmful side effects

Gut microbes could protect us from toxic ‘forever chemicals’

Novel modelling links sea ice loss to Antarctic ice shelf calving events

Scientists can tell how fast you're aging from a single brain scan

U.S. uterine cancer incidence and mortality rates expected to significantly increase by 2050

Public take the lead in discovery of new exploding star

What are they vaping? Study reveals alarming surge in adolescent vaping of THC, CBD, and synthetic cannabinoids

ECMWF - delivering forecasts over 10 times faster and cutting energy usage by 1000

Brazilian neuroscientist reveals how viral infections transform the brain through microscopic detective work

Turning social fragmentation into action through discovering relatedness

Cheese may really be giving you nightmares, scientists find

Study reveals most common medical emergencies in schools

Breathable yet protective: Next-gen medical textiles with micro/nano networks

Frequency-engineered MXene supercapacitors enable efficient pulse charging in TENG–SC hybrid systems

Developed an AI-based classification system for facial pigmented lesions

[Press-News.org] HOXA9 tracking reveals RBM5 dual function and therapeutic potential for acute myeloid leukemia