Dr Jamile Shammo is a Professor of Medicine and Pathology in the Department of Internal Medicine, Division of Hematology, Oncology and Cell Therapy, at Rush Medical College.
studies molecular mechanisms leading to cancer, blood diseases, sickle cell anemia, hemophilia and other coagulopathies.
Dr. Angela Fleischman is an Associate Professor of Medicine in the Division of Hematology/Oncology at the University of California, Irvine. The Fleischman Lab is known nationwide for its research on the role of nutrition in MPN.Identify what is important to you and what you are passionate about, as long as you keep your eye on that everything else is just details.
When Bruce Glover was diagnosed with a rare blood cancer, he quickly realised life would not be the same.
“My doctor put her hand on my shoulder and said, ‘I’m your friend for life,’ and I realised at this stage it wasn’t going to be cured,” he said.
The 69-year-old runs his own business on the Gold Coast but has found it harder to stay on top of his game since being diagnosed with myelofibrosis in 2018.
“I used to be like the Energiser battery — I could outrun anyone in business, work and so forth,” he said.
“I can’t do the things I used to do, which gets extremely frustrating.”
But a recent stroke of luck for a team of Adelaide researchers could lead to the first possible effective treatment for the rare and crippling blood cancer.
Myelofibrosis, a type of bone marrow cancer, affects about one in 100,000 people in Australia and can often lead to complete marrow failure or even acute leukaemia.
Daniel Thomas, leader of the Myeloid Metabolism Lab at the South Australian Health and Medical Research Institute (SAHMRI), has been searching for better therapies for primary myelofibrosis for three years.
“It progresses over a period of three to five years, resulting in severe fibrosis of the marrow, and it can sometimes change into acute leukaemia where patients get sick extremely quickly,” he said.
Dr Thomas and his team of Adelaide researchers were trying to create a tool to help understand how the disease impacted the human body, but what they ended up discovering was much more extraordinary.
“As we were making an antibody to try and understand how calreticulin protein worked inside stem cells … we were completely shocked to find out that it actually stopped their (cancer cells’) growth,” he said.
Dr Thomas first assumed the results were a mistake.
“I said, ‘We have to repeat this. This is too good to be true,'” he said.
But after multiple tests, he was convinced they had found a treatment for what is often considered an “undruggable mutation”.
“And low and behold, the antibody actually stopped these [cancer cells] growing out but did not stop a single normal healthy stem cell growing,” Dr Thomas said.
The new antibody is currently being prepared for early-phase clinical trials set to run in South Australia later this year.
Dr. Catriona Jamieson is Professor of Medicine in the Division of Hematology-Oncology, Deputy Director of UC San Diego Moores Cancer Center, Co-Lear of Hematologic Malignancies Program, and Director of Stem Cell Research at UC San Diego Moores Cancer Center.
Dr. Nicole Kucine is an Associate Professor of Clinical Pediatrics at Weill Cornell Medicine and Associate Pediatrician at NewYork-Presbyterian/Weill Cornell Medical Center. She is an advisor of our Pediatric & Young Adult MPNs focus.
Ann Mullally, MD is an Associate Professor, Medicine, Harvard Medical School, an Attending Physician, Leukemia Program, Medical Oncology, Dana-Farber Cancer Institute and an Associate Physician, Hematology, Brigham And Women’s Hospital. She is a translational cancer researcher in the field of myeloid malignancies, with a focus on myeloproliferative neoplasms (MPN).
As a female in this area of medicine, what advice would you give women grappling with career choices in hematology and medical research?
03-14-2022 11:27 AM CET
Press release from Orion Market Research
The global post polycythemia vera myelofibrosis (PPV-MF) market is anticipated to grow at a significant CAGR during the forecast period (2021-2027). Post-polycythemia vera myelofibrosis is a form of the myeloproliferative neoplasm and is also called chronic idiopathic myelofibrosis. It is a rare chronic blood cancer. People with myelofibrosis (MF) have a defect in their bone marrow that results in an abnormal production of blood cells which causes scar tissue to form. The major factor driving the growth of the market is the increasing prevalence of polycythemia vera (PV) across the globe.
According to the Leukemia & Lymphoma Society, PV is more prevalent among Jews of Eastern European descent than other Europeans or Asians. However, the incidence of PV is about 2.8 per 100,000 population of men and about 1.3 per 100,000 population of women of all races. Additionally, an estimated number of people in a population with PV is about 22 cases per 100,000 people. Furthermore, PV is mostly diagnosed at the average age of 60 to 65 years and it is uncommon in individuals younger than 30 years. Hence, the increasing prevalence of PV is driving the growth of the global post polycythemia vera myelofibrosis (PPV-MF) market.
To Request a Sample of our Report on Post Polycythemia Vera Myelofibrosis (PPV-MF) Market: https://www.omrglobal.com/request-sample/post-polycythemia-vera-myelofibrosis-ppv-mf-market
Researchers led by Christopher Garcia of the Ludwig Center at Stanford University have solved the long-sought structure of a large signaling protein involved in responses to infection, inflammation, the generation of immune cells, and when dysregulated by mutation-; the emergence of blood cancers known as myeloproliferative neoplasms. Published in the journal Science, the structure reveals the mechanism by which this protein, Janus kinase (JAK), transmits signals sent by immune cell growth factors called cytokines.
That structural information has direct implications for the development of new drugs for myeloproliferative neoplasms, which are currently treated with drugs often referred to as “jakinibs” that target all JAK proteins, not just the mutants that drive cancer. This broad targeting of JAK proteins causes side effects that include anemia and thrombocytopenia, a blood clotting disorder.
“Our model of JAK structure gives us an atomic blueprint for how one could make mutant-selective medicines to treat these cancers,” said Garcia. “This is the essence of basic discovery biology leading to translational insights.”
Cytokines signal through receptors found on the cell surface that thread through the cell’s outer membrane into its cytoplasm. Each receptor has attached to its cytoplasmic tail, a single JAK protein in an inactive state. Each cytokine protein binds two of these receptors, drawing their attached JAKs together.
“When the JAKs are brought close together, they activate one another,” Garcia explained. “That’s the activated complex that gets the signaling engine running.”
Each JAK phosphorylates-; or adds a phosphate molecule-; to a specific spot on its partner. So activated, the JAKs then phosphorylate the cytokine receptor to which they’re attached, drawing a protein known as STAT to the complex. It is this complex that transmits the cytokine’s growth-promoting signal.
The structure solved by Garcia’s lab, which has pursued this prize for more than two decades, is of the JAKs in their juxtaposed and activated state.
“Small pieces of the JAK structure had been published over the years-; a toe here, a finger there, an ear there-; but nobody had seen what the whole body looked like, so to speak,” said Garcia.
The full structure shows that when drawn together by the cytokine, the JAKs meet at a roughly flattened region in their middle. The change induced by the oncogenic JAK mutation-; swapping the smaller amino acid valine for the much larger phenylalanine-; falls in the middle of this region. The mutation alters the flat interface between the JAKs, creating a sort of ball and socket connection between the two that makes them adhere far more firmly to one another.
“When people have this mutation-; the most classical mutation in blood cancers-; the JAKs come together and start working all the time because there’s like a little dab of glue in there that’s bringing them together even when there’s no cytokine around,” Garcia said. They thus continuously transmit growth signals, driving cell proliferation.
The finding opens the door to developing small molecules that disrupt the ball-and-socket connection of the mutant JAKs. Such drugs would not affect normal JAK proteins and would, therefore, be less likely to have toxic side effects.
Garcia and his colleagues solved the structure of the mouse JAK-1 protein. The “V617F” mutation that drives myeloproliferative neoplasms is, however, found in its cousin, JAK-2. But, Garcia says, the two are sufficiently alike to share the same signaling mechanism.
Garcia’s group is now working on developing drugs to target V617F mutant JAKs and capturing the structure of the larger JAK-STAT complex and that of the complexes formed between different types of JAKs, which are also involved in cytokine signaling.
Claire Harrison, MD, DM, FRCP, FRCPath is a Professor of Hematology at the Guy’s and St. Thomas’ NHS Foundation Trust in London, UK. Prof. Harrison became a Consultant at the Guy’s and St. Thomas’ NHS Foundation Trust in 2001, where she is now a Clinical Director.