Latest news with #leukemia
Medscape
18 hours ago
- Health
- Medscape
Genetics or Microenvironment: What Drives CLL Progression?
MILAN — Is chronic lymphocytic leukemia (CLL) progression primarily driven by genetic mutations or by external cues from the tumor microenvironment? Despite major strides in targeted therapies, CLL remains incurable, prompting renewed scrutiny of whether intrinsic genetic alterations or extrinsic cellular forces hold the key to more effective, lasting treatment. This central question took the spotlight at the 2025 European Hematology Association (EHA) Annual Congress, sparking a lively debate among leading CLL researchers. Most therapies have targeted intrinsic molecular features of leukemic cells, such as BCL2 and BTK. But the lack of robust responses to immunotherapy suggests that external factors such as the tumor microenvironment may also play a role. 'The debate dates back to at least 1999,' said session chair Silvia Deaglio, MD, PhD, director of the Immunogenetics and Transplant Biology Service, City of Health and Science of Turin, Italy in an interview with Medscape Medical News . 'That year, two landmark papers showed that mutations in IGHV [immunoglobulin heavy chain variable region] genes were a favorable prognostic marker, supporting a genetic model. But those same studies also identified an unfavorable prognostic marker in a molecule linked to how CLL cells interact with their environment, suggesting a role for the microenvironment as well.' Genetic Drivers Take Center Stage Eugen Tausch, MD, PhD, researcher at the University of Ulm, Germany, argued in favor of genetics as the primary driver. 'All CLLs have at least one genetic driver, and IGHV mutation status is a fundamental and stable biomarker,' he said. This mutation status affects multiple cellular mechanisms, including immune evasion, anti-apoptotic signaling, and B-cell receptor function. It also modulates how cells respond to cues from their environment, reinforcing the need to consider IGHV when studying microenvironmental influences. But IGHV is just one piece of the puzzle, Tausch added. More than 200 genetic drivers have been identified in CLL. Roughly 90% of cases harbor at least one gene mutation or chromosomal aberration that affects DNA repair, cell cycle regulation, metabolism, RNA processing, and intracellular signaling. 'These alterations have clear clinical implications,' he said. 'Resistance to BTK and BCL2 inhibitors often arises through mutations at the drug-binding site, establishing a direct link between genetics and therapy failure.' Understanding and tracking clonal genetic evolution is thus key to risk stratification, treatment planning, and anticipating disease trajectory, he concluded. The Microenvironment's Role in Early Disease Although CLL has long been seen as a genetically driven malignancy, new data suggest a more nuanced picture in which the tumor microenvironment influences early clonal dynamics. 'We know mutations drive disease progression, especially under therapeutic pressure, but the triggers of these mutations are less clear,' said John Gribben, MD, DSc, Hamilton Fairley Professor of Medical Oncology at Barts Cancer Institute, Queen Mary University of London, UK, who argued in favor of the microenvironment. Accumulation of mutations with age, oxidative stress, antigenic stimulation, and rare inherited factors have all been proposed, but these likely act in concert with tumor microenvironment signals to promote early clonal expansion, he explained. In lymph nodes and bone marrow, CLL cells interact with a milieu of stromal and nurse-like cells, dysfunctional T cells, and dendritic cells, along with a variety of cytokines and chemokines. Recent studies have shown that early clonal evolution primarily occurs in lymph nodes and is associated with a suppressed T-cell inflammatory response. A small subpopulation of lymph node-activated CLL cells engages with the microenvironment to drive disease progression and possibly influence mutation patterns. Moreover, therapies that disrupt microenvironmental interactions have shown efficacy by blocking B-cell receptor signaling and impairing chemokine-mediated trafficking. Even while advocating for the microenvironment's role, Gribben proposed a hybrid model. 'Genetic lesions set the stage, but microenvironmental forces shape their emergence and survival. Early on, extrinsic factors dominate. Later, clonal evolution and genetic resistance take over.' A New Paradigm of Coexistence Both speakers emphasized the need to move beyond binary models of CLL progression. 'The data support a dynamic interplay,' Deaglio told Medscape Medical News . 'The long-term coexistence between leukemic cells and their environment in CLL alters both cell behavior and immune function.' She noted that the T-cell compartment becomes tolerogenic, showing expansion of regulatory T cells and memory effector cells, among other markers. The debate also touched on the progression from monoclonal B-cell lymphocytosis to CLL and on Richter transformation, reinforcing the need for an integrated understanding of intrinsic and extrinsic disease drivers. Deaglio underlined that researchers are now exploring whether treatment-resistant patients could benefit from new drugs or combinations and whether therapy could eventually be administered for fixed durations rather than continuously until progression. 'Progression is genetically driven,' said Deaglio. 'But single-cell sequencing shows that some leukemic cells carry the features that enable future expansion a long time before the disease is diagnosed. Why some clones grow while others do not may depend on the environment they find themselves in.' Gribben concluded, 'To treat CLL effectively, and maybe reach a cure, we'll need to combine immune-based approaches with current targeted therapies.' Deaglio reported no relevant financial relationships. Tausch reported industry affiliations with AbbVie, BeiGene, Lilly, AstraZeneca, Roche, and Janssen-Cilag. Gribben reported research funding from AstraZeneca, BMS/Celgene, and Janssen; clinical trials with AbbVie, Celgene, Epizyme, Gilead, Genmab, Janssen, Merck, MorphoSys, Pharmacyclics, Regeneron, Roche/Genentech, and Takeda; consultancy for AbbVie, Amgen, AstraZeneca, BeiGene, BSM/Celgene, Janssen, Kite Gilead, and Takeda; and honoraria from AbbVie, AstraZeneca, BeiGene, BSM/Celgene, Janssen, Kite Gilead, and Novartis.
Daily Mail
19 hours ago
- Health
- Daily Mail
The subtle change to your skin that could mean deadly blood cancer, according to doctor
Bruising without explanation should never be ignored as it can be a little-known sign of deadly blood cancer, a doctor has warned. According to GP Dr Sermed Mezher, the small purple, brownish marks could in fact indicate a range of hidden diseases, including thyroid conditions and liver failure. In an Instagram clip posted to Dr Mezher's page, where he has over 349,000 followers, he revealed an image of a woman's legs that illustrated the type of bruising to watch out for. 'Bruising without a clear explanation—such as not recalling an injury or impact—is a potential sign that something more serious may be going on beneath the surface and should not be ignored',' he said in the video. 'Frequent or severe bruising without cause can be a red flag.' Social media users took to the comment section to echo Dr Mezher's warning. 'My dad had small bruises all over his legs (before) leukemia. May he rest in peace,' said one. Another, @nay_theposho, said: 'Before my diagnosis (acute T-cell leukemia at ten) I had all these weird things happen. View this post on Instagram A post shared by Sermed Mezher (@drsermedmezher) 'Mum remembers I had started getting chubby but I had lost all the weight so she didn't think about it, nor my numerous bruises since I was a clumsy child. 'Then my breathing got funny and I was seen four times before they officially diagnosed me.' 'A very key sign that had been missed was a strange purple bruise. Always be vigilant.' Excessive bruising is common in blood cancer due to a deficiency in a type of blood cell called platelets, which help the blood to clot after an injury. A lack of these cells mean the body cannot stop blood vessels from bleeding under the skin, leading to bruising. Other signs of blood cancer include fevers, night sweats, weight-loss, tiredness and swollen lymph nodes, Dr Mezher added. Blood cancer is not the only potentially fatal condition bruising can be a sign of. If it is accompanied with yellowing of the skin and whites of the eyes, it can also be a tell tale symptom of liver disease that kills over 12,000 Britons and 50,000 Americans every year, he warned. When the liver is damaged, it cannot produce sufficient amounts of proteins needed to help the blood clot. Meanwhile excessive bleeding from other areas like the nose gums or during menstrual periods it could be a sign of a bleeding disorder such as hemophilia. This is when someone is prone to excessive bleeding because the body is unable to clot. These conditions are estimated to affect 7,625 women and 4,310 men in the UK, but many thousands remain undiagnosed, according to The Haemophilia Society. 'If you also can't tolerate the cold and are gaining weight easily and are tired all the time, it could be a sign of a thyroid problem,' Dr Mezher added. This is a medical condition that prevents the thyroid—the little, butterfly-shaped gland in the neck—from making the right amount of hormones, leading to a range of symptoms including muscle weakness, depression, and brain fog. It's estimated that one in 20 people in the UK have a thyroid problem, with women six times more likely to suffer from the condition than men. 'If you also have hypermobility or stretchy skin, then it could be a sign of a connective tissue disorder like Ehlers Danlos syndrome (which can cause life-threatening complications in a rare cases),' he added. 'Getting evaluated by a healthcare professional can help rule out serious causes and insure that, if treatment is needed, it begins early.
The Sun
a day ago
- Politics
- The Sun
Tragic cancer-stricken girl, 7, who fled wartorn Ukraine for leukaemia treatment in Israel killed in Iran missile blitz
A SEVEN-year-old girl who fled the war in Ukraine to receive life-saving leukaemia treatment in Israel has been tragically killed. Nastia Borik, her grandmother and two young cousins were all reported dead following the Iranian blitz on a Bat Yam apartment building in Tel Aviv on Sunday. 6 6 6 Her mother Maria Peshkurova, 30, remains missing, the Times of Israel reports. The attack, which is believed to have wounded 180 people and killed at least six, comes amid six nights of heavy missile exchange between the two warring countries. Nastia Borik arrived in Israel in 2022 with her mother, grandmother, Lena Peshkurova, 60, and two of her cousins, Konstantin Totvich, 9, and Ilya Peshkurov, 13, to seek life-saving treatment for Leukemia. The girl's father, Artem, reportedly stayed in Ukraine to fight in the war against Russia. He could not accompany his daughter due to a government order barring men under the age of 60 from leaving the country during the conflict. Her tragic killing comes as tensions between Israel and Iran have reached cataclysmic heights, as a major Israeli hospital and an Iranian nuclear reactor were both blitzed this morning. Soroka Hospital in Beersheba was severely damaged when it was struck by an Iranian ballistic missile, with Israel reporting around 70 casualties overnight - some serious. The IDF confirmed it attacked an "inactive" plutonium nuclear reactor in Arak to "prevent it from being restored and used for nuclear weapons". After days of speculation, Trump on Tuesday night approved plans to attack Iran, but is holding off in case Tehran agrees to abandon its nuclear programme, reports the Wall Street Journal. If given the go-ahead, the plans would see the US join Israel in pounding Iran's nuke sites - which Tehran has warned would spark "all out war". Chilling vid shows Israeli school bus blown to bits by Iranian missile in madcap Ayatollah's death-throw retaliation The UK is yet to declare whether it would stand with the US should Trump decide to go ahead with military action. But Sir Keir Starmer has been warned by Attorney General Lord Hermer that the UK's involvement could be illegal. It comes as Sir Keir held a Cobra crisis meeting on Wednesday with a potential US-led strike reportedly being discussed. Trump has become much more vocal on the conflict, though refuses to confirm his plans: "I may do it, I may not do it," he said on Wednesday. If the US does collaborate in the attacks, Iran's Fordow nuclear development area could be its first target. A fearsome 15-ton mega bomb known as a Massive Ordnance Penetrator (MOP) bomb could be used to strike the core of the plant, which Israel is unable to reach with its own weapons. Speaking to reporters from the Oval Office Trump acknowledged the US is the only nation capable of blitzing the key nuke site. But he added: "That doesn't mean I'm going to do it - at all." Trump also fired a two-word warning to Iran's Supreme Leader after revealing Tehran was trying to return to the negotiating table. When a White House reporter asked Trump about Ayatollah Ali Khamenei's declaration that he will "never surrender", Trump simply responded: "Good luck." Trump even directly threatened Khamenei as he said the US knows where he is hiding but will not kill him 'for now'. Khamenei responded by saying: "The battle begins. This nation will never surrender. 'America should know that any military intervention will undoubtedly result in irreparable damage.' US officials indicated the next 24 to 48 hours will be crucial in determining whether diplomacy could ever be achieved with Iran, ABC News reports. It comes as warmongering Russia ironically warned the world sits "on the brink of catastrophe" as the raging Middle East conflict entered day six. 6 6 6
Health Line
a day ago
- Health
- Health Line
Survival Rates and Outlook for Acute Myeloid Leukemia (AML)
• Advancements in cancer treatments and doctors' understanding of acute myeloid leukemia (AML) mean that more and more people survive the condition each year. • The 5-year overall survival rate for AML is 29.5 percent, but children generally have a higher remission rate after initial treatment compared to adults. • Factors such as age, AML subtype, and treatment response significantly influence survival rates, with treatment being less effective for individuals over 60. AML is a type of cancer that affects the bone marrow and blood. It's known by various names, including acute myelogenous leukemia and acute non-lymphocytic leukemia. AML is one of the most common leukemia types in adults. Doctors call AML ' acute ' because the condition can progress rapidly. The term ' leukemia ' refers to cancers of the bone marrow and blood cells. The word myeloid, or myelogenous, refers to the cell type it affects. Myeloid cells are precursors to other blood cells. Usually, these cells go on to develop into red blood cells (RBCs), platelets, and special types of white blood cells (WBCs). But in AML, they aren't able to develop normally. When a person has AML, their myeloid cells mutate and form leukemic blasts. These cells don't function as normal cells do. They can keep the body from making normal, healthy cells. Eventually, a person will start to lack RBCs that carry oxygen, platelets that prevent easy bleeding, and WBCs that protect the body from diseases. That's because their body is too busy making the leukemic blast cells. The result can be deadly. However, for many people, AML is a treatable disease. What are the survival rates for AML? Every year, doctors diagnose an estimated 20,240 cases of AML in the United States. An estimated 11,400 deaths occur annually because of the disease. Most people with AML receive chemotherapy treatments. These medications rapidly kill dividing cells, such as cancer cells. Chemotherapy can lead to remission, which means a person doesn't have symptoms of the disease and their blood cell counts are in a normal range. According to the American Cancer Society (ACS), around 90 percent of people with an AML type known as acute promyelocytic leukemia (APL) will go into remission after 'induction' (first round) of chemo. For most other types of AML, the remission rate is around 67 percent. People older than age 60 don't typically respond to treatment as well, with about half of them going into remission after induction. Some people who go into remission stay in remission. Still, for many, AML can return over time. The 5-year overall survival rate for AML is 29.5 percent, according to the National Cancer Institute (NCI). This means that an estimated 29.5 percent of people in America living with AML are still living 5 years after their diagnosis. Children with AML In general, children with AML are seen as lower risk than adults. Around 85 to 90 percent of children with AML will go into remission after induction therapy. AML will return in some cases. The 5-year-survival-rate for children with AML is 65 to 70 percent. What factors influence survival rate? The outlook and prognosis for acute myeloid leukemia varies widely. Doctors consider many factors when giving someone a prognosis, such as the person's age or type of AML. Much of the outlook is based on the outcomes and analysis of: blood tests imaging studies cerebrospinal fluid (CSF) examinations bone marrow biopsies Some people with a poor prognosis live many more years than a doctor predicts, while others may not live as long. What effect does age have on survival rate? The median age of a person diagnosed with acute myeloid leukemia is 68 years old. Age can be a major factor in determining AML treatment response. Doctors know that survival rates for those diagnosed with AML are more promising for people under age 60. This could be for a number of reasons. Some people older than 60 may have chronic conditions or other health issues. This can make it difficult for their bodies to handle the strong chemotherapy medications and other cancer treatments associated with acute myeloid leukemia. Moreover, many older adults with AML don't receive treatment for the condition. A 2018 study found that 25 percent of adults diagnosed with AML did not get chemotherapy. Researchers noted that older age and having other major health problems decreased the likelihood of receiving chemo, as well as being female and having a lower income status. A 2015 study found that only 40 percent of people ages 66 and up received chemotherapy within 3 months of diagnosis. Research published in 2020 suggests that despite the differences in treatment response among different age groups (or cohorts), overall 5-year survival rates are improving for all groups. However, researchers note that those rates drop off significantly as people with the condition get older. Age 5-year survival rate Children under the age of 14 65 to 70 percent Ages 15 to 34 52 percent Ages 35 to 54 37 percent Ages 55 to 64 20 percent Ages 65 to 74 9 percent What effect does AML type have on survival rate? Doctors often classify the different subtypes of AML, because the subtype affects a person's health outlook and the best course of treatment. This is because AML does not follow the stages of other cancers with tumors. The various types may require different forms of treatment and may affect the potential survival rate. According to the French-American-British classification of AML, subtypes include: M0. Undifferentiated acute myeloblastic leukemia M1. Acute myeloblastic leukemia with minimal maturation M2. Acute myeloblastic leukemia with maturation M3. Acute promyelocytic leukemia (APL) M4. Acute myelomonocytic leukemia M4 eos. Acute myelomonocytic leukemia with eosinophilia M5. Acute monocytic leukemia M6. Acute erythroid leukemia M7. Acute megakaryoblastic leukemia Your oncologist will tell you what subtype you have. What effect does treatment response have on survival rate? Treatment works better for some people than others. If a person receives chemotherapy treatments and their cancer doesn't come back within 5 years, they're usually considered 'cured.' If a person's cancer comes back or doesn't respond to treatments at all, their treatment outcome isn't as favorable. Some people also cannot tolerate treatment and thus do not get the full benefit if it's stopped early or has to be modified. Treatment depends on the person's age and overall health, which also affects survival.
CBS News
2 days ago
- Health
- CBS News
This 9-year-old cancer patient has relapsed 7 times, but now Alex's Lemonade Stand is helping her recover
A childhood cancer diagnosis can be unpredictable. What will the treatment be? Will it work? Will my child relapse? Ailani Myers, 9, has relapsed seven times, but her motto remains the same. "We've always said, you know, we're a family, we're a team, and we do what we have to do," Princecine Myers, Ailani's mother, said. "It means even if we don't want to do it, we still have to do it anyways," Ailani Myers said. Pretty wise words from a 9-year-old who has been through more than most adults. It all started during a visit with family in Texas. "She had a rash," Princecine Myers said. "I thought was a rash. Come to find out, it was petechiae. And, you know, they were like, 'Oh, it's just petechiae, really no big deal. But if you want to have blood work done, you need to take her to the emergency room.'" Princecine Myers' motherly instinct told her to get the bloodwork, and it showed a shocking diagnosis — leukemia. It was a rare form of leukemia: one that made Ailani high-risk. The family moved to Baltimore and started a very long journey. "So when we got to Baltimore, we did her first bone marrow transplant," Ailani's father, Kurt Myers, said. "She relapsed a year later, then she did CAR T-cell therapy for the first time, relapsed nine months later. Then we did a second bone marrow transplant, and she relapsed 60 days later. Then we did the second CAR T-cell therapy. She relapsed 60 days after that. Then we did her third CAR T-cell therapy, and I think she relapsed at nine months, and then we did her fourth CAR T-cell therapy. And they saw evidence, maybe evidence of disease, at her nine-month test." And even though that could have been a false positive, that meant another CAR T-cell treatment. That was in January, and since then, there's been no evidence of disease. Ailani's been through even more than her dad listed. She's had other treatments and was part of many clinical trials. "Everything except her first two major treatments have been clinical trials, and they've been completely foundational and critical to where we're at now and her looking as well as she looks," Kurt Myers said. And she looks beautiful. Ailani has been part of Alex's Lemonade Stand Foundation's "Flashes of Hope" program. It pairs kids and families with photographers. "They've watched her grow up and memorialized so many steps along the way," Kurt Myers said. "She looked a little different on the outside, but she always had the same fierceness and drive and heart and determination, and just so sweet and kind," Princecine Myers said.
