Chemo-boosting drug discovered for leukaemia – Drug Target Review – Drug Target Review
By daniellenierenberg
Drugs developed to treat heart and blood vessel problems could be used to treat leukaemia
Drugs developed to treat heart and blood vessel problems could be used in combination with chemotherapy to treat an aggressive form of adult leukaemia.
Researchers at the Francis Crick Institute, Kings College London and Barts Cancer Institute discovered that acute myeloid leukaemia (AML) causes bone marrow to leak blood, preventing chemotherapy from being delivered properly.
Drugs that reversed bone marrow leakiness boosted the effect of chemotherapy in mice and human tissue, providing a possible new combination therapy for AML patients.
To study how AML affects bone marrow, the researchers injected mice with bone marrow from AML patients. Later, they compared their bone marrow with healthy mice using a technique called intravital microscopy that allows you to see biological processes in live animals. They found that pre-loaded fluorescent dyes leaked out of the bone marrow blood vessels in AML mice, but not healthy mice.
Next, the team tried to understand what caused the bone marrow in AML mice to become leaky by studying molecular changes in the cells lining the blood vessels. They found that they were oxygen-starved compared to healthy mice, likely because AML cells use up a lot of oxygen in the surrounding tissue. In response to a reduction in oxygen, there was an increase in nitric oxide (NO) production a molecule that usually alerts the body to areas of low oxygen.
As NO is a muscle relaxant, the team suspected that it might be causing bone marrow leakiness by loosening the tight seams between cells, allowing blood to escape through the gaps. By blocking the production of NO using drugs, the team were able to restore bone marrow blood vessels in AML mice, preventing blood from leaking out. Mice given NO blockers in combination with chemotherapy had much slower leukaemia progression and stayed in remission much longer than mice given chemotherapy alone.
When the vessels are leaky, bone marrow blood flow becomes irregular and leukaemia cells can easily find places to hide and escape chemotherapy drugs, said researcher Dr Diana Passaro. Leaky vessels also prevent oxygen reaching parts of the bone marrow, which contributes to more NO production and leakiness.
By restoring normal blood flow with NO blockers, we ensure that chemotherapy actually reaches the leukaemia cells, so that therapy works properly, she added.
In addition to ensuring that chemotherapy drugs reach their targets, the team also found that NO blockers boosted the number of stem cells in the bone marrow. This may also improve treatment outcomes by helping healthy cells to out-compete cancerous cells.
The team also found that bone marrow biopsies from AML patients had higher NO levels than those from healthy donors, and failure to reduce NO levels was associated with chemotherapy failure.
Our findings suggest that it might be possible to predict how well people with AML will respond to chemotherapy, said Dr Dominique Bonnet, senior author of the paper and Group Leader at the Francis Crick Institute.
Weve uncovered a biological marker for this type of leukaemia as well as a possible drug target. The next step will be clinical trials to see if NO blockers can help AML patients as much as our pre-clinical experiments suggest.
We found that the cancer was damaging the walls of blood vessels responsible for delivering oxygen, nutrients, and chemotherapy. When we used drugs to stop the leaks in mice, we were able to kill the cancer using conventional chemotherapy, said Dr Passaro. As the drugs are already in clinical trials for other conditions, it is hoped that they could be given the green light for AML patients in the future.
Excerpt from:
Chemo-boosting drug discovered for leukaemia - Drug Target Review - Drug Target Review
- 5 year old boy from Iraq undergoes world's first of its kind bone marrow transplantation in India - The Times of India - March 31st, 2025
- Superior outcomes of haploidentical hematopoietic cell transplantation over chemotherapy in AML patients 55 years or older - Nature.com - March 31st, 2025
- Blood and Marrow Transplantation and Cellular Therapy Center - NYU Langone Health - March 22nd, 2025
- Bone Marrow Transplantation Market Poised to Achieve USD 14,336 Billion by 2031 - Persistence Market Research - openPR - March 22nd, 2025
- BioRestorative Therapies to Report 2024 Financial Results and Host Conference Call on March 27, 2025 - The Manila Times - March 22nd, 2025
- Man Cured Of Sickle Cell Disease In New York Thanks To New Gene Therapy - Forbes - March 22nd, 2025
- Boost in cancer treatment: PGI working on lab for stem cell, gene therapies - The Times of India - March 22nd, 2025
- Clonal dynamics and somatic evolution of haematopoiesis in mouse - Nature.com - March 11th, 2025
- Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow -... - March 11th, 2025
- TET2 deficiency increases the competitive advantage of hematopoietic stem and progenitor cells through upregulation of thrombopoietin receptor... - March 11th, 2025
- Garuda Therapeutics Closes $50 Million Series A-1 Financing to Advance Off-the-Shelf Blood Stem Cell Therapies - GlobeNewswire - March 11th, 2025
- Abu Dhabi Stem Cells Center and Yas Clinic first in UAE to receive AABB accreditation for haematopoietic progenitor cell collection - Abu Dhabi Media... - March 11th, 2025
- Discovery of lung-based blood stem cells may transform transplant therapies - Medical Xpress - March 1st, 2025
- VUMC part of new study validating curative therapy for sickle cell disease - VUMC Reporter - March 1st, 2025
- What Is the Role of MRD Testing Before HSCT in MDS/MPN? - DocWire News - March 1st, 2025
- Melphalan-based conditioning with post-transplant cyclophosphamide for peripheral blood stem cell transplantation: donor effect - Nature.com - March 1st, 2025
- Mesenchymal Stem Cells Market Projected to Reach USD 11.26 Billion by 2034, Growing at a CAGR of 12.9% - openPR - March 1st, 2025
- See snazzy slugs in all their luminous glory Februarys best science images - Nature.com - March 1st, 2025
- On the origin of neutrophils - Nature.com - March 1st, 2025
- Four-year-old donates stem cells to save her baby sister from blood cancer in Odisha - The Hindu - February 20th, 2025
- Effect of pre-transplant cytoreductive therapy on the outcomes of patients with MDS or secondary AML evolving from MDS undergoing allo-HSCT: a... - February 20th, 2025
- A heart disease trigger that lurks inside bone marrow - Harvard Health - February 20th, 2025
- 4-year-old donates stem cells to save sister as SCB performs first-of-a-kind bone marrow transplant in Odisha - OTV News - February 20th, 2025
- KU Cancer Center recognized for transplant that saved 1-year-olds life - WDAF FOX4 Kansas City - February 20th, 2025
- Orca-T With RIC Is Safe in Advanced Hematologic Malignancies - OncLive - February 20th, 2025
- SCB conducts Odisha's first bone marrow transplant on two-year-old - The New Indian Express - February 20th, 2025
- Bahrain's pioneering use of sickle cell disease treatment hailed by medical experts - The National - February 20th, 2025
- Cancer survivor is the first monumental bone marrow transplant patient in Baton Rouge in 8 years - NOLA.com - February 11th, 2025
- Autologous Cell Therapy Market to Hit Valuation of US$ 44.55 Billion By 2033 | Astute Analytica - GlobeNewswire - February 11th, 2025
- Nanoparticle that cuts middlemen could improve stem cell therapy - Futurity: Research News - January 31st, 2025
- GATA2 mutated allele specific expression is associated with a hyporesponsive state of HSC in GATA2 deficiency syndrome - Nature.com - January 31st, 2025
- Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy - Science - January 31st, 2025
- How the bone marrow microbiome responds to immunotherapy - Chemical & Engineering News - January 31st, 2025
- My Experience With Stem Cell Therapy: Snake Oil or Silver Bullet? - GearJunkie - January 31st, 2025
- Hematopoietic Stem Cell Transplantation - StatPearls - NCBI ... - January 22nd, 2025
- Doctors retrieve stem cells from 20-month-old to treat thalassaemic sister - The Times of India - January 22nd, 2025
- YolTech Therapeutics to Initiate a Clinical Trial for YOLT-204, a First-in-Class Bone Marrow-Targeted In Vivo Gene Editing Therapy for -Thalassemia -... - January 22nd, 2025
- School of Medicine professor receives grant to study improved cancer treatments - Mercer University - January 14th, 2025
- 1st stem cell therapy, new HIV drug approved - ecns - January 5th, 2025
- Suppression of thrombospondin-1mediated inflammaging prolongs hematopoietic health span - Science - January 5th, 2025
- A pilot raced through the airport to surprise an old friend: the woman who saved his life - CNN - December 27th, 2024
- Types of Stem Cell and Bone Marrow Transplants - December 27th, 2024
- Explained: What is mesenchymal stem cell therapy? - Drug Discovery News - December 18th, 2024
- Stem Cell Transplants Offer New Hope for Saving the Worlds Corals - Technology Networks - December 18th, 2024
- Scientists Present Research on Novel Cancer Therapies at ASH - City of Hope - December 18th, 2024
- Navigating CAR-T cell therapy long-term complications - Nature.com - December 18th, 2024
- High-dose chemotherapy followed by autologous stem cell transplant ineffective for patients with mantle cell lymphoma - News-Medical.Net - December 18th, 2024
- Stem Cell Therapy Market Is Expected To Reach Revenue Of - GlobeNewswire - December 18th, 2024
- The Importance of Cellular Therapy in the Clinical Case of a Young Man With a Challenging Precursor B-cell Lymphoblastic Leukemia - Cureus - December 18th, 2024
- A search for the perfect match, Apex six year old in need of donor - CBS17.com - December 18th, 2024
- New insights into survival of breast cancer cells in the bone marrow - News-Medical.Net - December 9th, 2024
- Cellular trafficking and fate mapping of cells within the nervous system after in utero hematopoietic cell transplantation - Nature.com - December 9th, 2024
- Saving lives, one stem cell at a time - Texas A&M The Battalion - December 9th, 2024
- Turn Biotechnologies Announces Landmark Study to Assess Effectiveness of ERA Therapy in Restoring Bone Marrow - PR Newswire UK - December 9th, 2024
- Orca Bio Presents Three-Year Survival Data with Orca-T in Patients with Hematological Malignancies at the 66th ASH Annual Meeting - Yahoo Finance - December 9th, 2024
- You are the match. How UNC student honored her late grandfather with life-saving effort - Raleigh News & Observer - November 29th, 2024
- scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes... - November 29th, 2024
- Atlanta pilot with an aggressive cancer finds lifesaving help from a stranger and a simple test - The Atlanta Journal Constitution - November 29th, 2024
- Researchers have brought the promise of stem cell therapies closer to reality - The Week - November 29th, 2024
- Bone Marrow Donors Can Be Hard to Find. One Company Is Turning to ... - November 15th, 2024
- Hematopoietic Stem Cells and Their Niche in Bone Marrow - November 15th, 2024
- Bone Marrow Transplant Program - Overview - Mayo Clinic - November 15th, 2024
- Bone Marrow Donors Can Be Hard to Find. One Company Is Turning to Cadavers - WIRED - November 15th, 2024
- More stem cells for sickle cell gene therapy readied with motixafortide - Sickle Cell Disease News - November 15th, 2024
- Skull bone marrow expands throughout life and remains healthy during aging, researchers discover - Medical Xpress - November 15th, 2024
- Adult skull bone marrow is an expanding and resilient haematopoietic reservoir - Nature.com - November 15th, 2024
- Evaluation of standard fludarabine dosing and corresponding exposures in infants and young children undergoing hematopoietic cell transplantation -... - November 15th, 2024
- Stem cells grown in space show super powers but theres a catch - Study Finds - November 15th, 2024
- Getting a Stem Cell or Bone Marrow Transplant - October 21st, 2024
- Acquisition of durable insulin-producing cells from human adipose tissue-derived mesenchymal stem cells as a foundation for cell- based therapy of... - October 21st, 2024
- 1.5 Lakh Indians Register To Save Lives: Join the Mission To Fight Blood Cancer - The Better India - October 21st, 2024
- How Stem Cell and Bone Marrow Transplants Are Used to Treat Cancer - October 13th, 2024
- Stem Cell (Bone Marrow) Transplants - MD Anderson Cancer Center - October 13th, 2024
- Donating Bone Marrow and Stem Cells: The Process and What To Expect - October 13th, 2024
- What to expect as a stem cell or bone marrow donor - October 13th, 2024
- Structural organization of the bone marrow and its role in ... - October 13th, 2024
- Stem cell donor from down the road saved my life after global search - BBC.com - September 23rd, 2024
- Awaiting the call: family hopes to find blood stem cell donor - Claremont Courier - September 23rd, 2024
- Michigan woman one of first in world to successfully receive bone marrow from deceased donor - WDIV ClickOnDetroit - September 23rd, 2024
- Next-generation stem cell transplant: Revolutionizing a lifesaving cancer therapy - The Business Journals - September 23rd, 2024
