Green Country Boy Battling Leukemia Keeps Hope Alive On Birthday

Metabolic Enzyme and Its Role in Myeloid Leukemia

And he hasn't stopped smiling. Bryce has leukemia and has been a trooper while fighting for nearly two years. Last spring, he was granted a Make-A-Wish trip and was able to see his dreams up close in San Diego. Now Bryce is undergoing yet another round of chemotherapy. Then doctors will decide on a bone marrow transplant. Bryce's sister, who is in fourth grade at Cleveland, is his bone marrow match. Teachers and friends say Bryce (or Little "Bebo" as his family calls him) is one of the happiest, sweetest boys you'll ever meet. His hometown must agree, too. A couple of weeks ago, as he headed back to Memphis for treatment, Cleveland decked itself out in "Blue for Bryce" to show support. The little one was so excited to see photos on Facebook of hundreds of classmates and townspeople in blue, that he told the staff at St. Jude all about how everyone did something special just for him, his mother said. More information at

But the best part of the day for Calisi was in the cockpit of the C-17 Globemaster III, where he stood in the emergency exit door and waved at the airmen below. "I like all the buttons," he said as he insisted on putting on his custom flight helmet. Training with C-17 instructor pilot Matt Tarnowski, Calisi planned a mission to Hawaii, where they would fly out of Honolulu. "He learns faster than a lot of my copilots," Tarnowski quipped as Calisi pointed to the different controls. Later in the afternoon, Calisi was curcumin cancer treatment scheduled to ride in a C-17 Globemaster III simulator. He also liked the military coins he collected throughout the day. His favorite so far was one from the 9th Air Refueling Squadron. "It's so cool and so big," Calisi said as he pulled it out of his flight suit pocket. Before the trip, though, Calisi helped the crews load a 2 1/2 ton truck onto the C-17. "He did a good job," said C-17 Loadmaster Kevin Knerr. More information at

Leukemia doesn't slow this 'pilot' as Make-A-Wish sends 'AJ' Calisi to Travis Air Force Base

As a result, mutant IDH proteins have been proposed as attractive drug targets for this common form of adult leukemia. Now a scientific team at Beth Israel Deaconess Medical Center (BIDMC) has generated a transgenic mouse model of the most common IDH2 mutation in human AML, and, in the process, answered a central question of whether these mutant IDH proteins are required for leukemia initiation and maintenance in a living organism. Currently published on-line in the journal Cell Stem Cell and scheduled to appear in print in March, these new findings confirm a potent oncogenic role for IDH2, and support its relevance as a therapeutic target for the treatment of this widespread blood cancer. Equally important, this transgenic model provides an important new tool for evaluating the pharmacological efficacy of potential mutant IDH2 inhibitors, either alone or in combination with other compounds. "The real hope is that we would one day be able to treat IDH2-mutant leukemia patients with a drug that targets this genetic abnormality," explains senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and the Cancer Research Institute at BIDMC and the George C. Reisman Professor of Medicine at Harvard Medical School. "Our transgenic animal model has now demonstrated that the IDH mutation contributes to the initiation of acute leukemia in vivo and that mutant IDH is essential for the maintenance of leukemic cells even in a genetic setting where mutant IDH is not required for cancer initiation." IDH1 and IDH2 proteins are critical enzymes in the TCA cycle, which is centrally important to many biochemical pathways. Mutated forms of these proteins gain a novel ability to produce 2-hydroxyglutarate (2HG), a metabolite that has been shown to accumulate at high levels in cancer patients and is therefore described as an "oncometabolite." "Our goal was to generate an animal model of mutant IDH that was both inducible and reversible," explains co-lead author Markus Reschke, PhD, an investigator in BIDMC's Cancer Research Institute and Research Fellow in the Pandolfi laboratory. "This enabled us to address an important unanswered question: Does inhibition of mutant IDH proteins in active disease have an effect on tumor maintenance or progression in a living organism?" Reschke and co-lead author Lev Kats, PhD, also a Research Fellow in the Pandolfi colorectal cancer treatment lab, studied two different models: a retroviral transduction model and a genetically engineered model in which IDH mice were crossed to mice harboring other leukemia-relevant mutations. In the first model, the IDH mutation was combined with the oncogenes HoxA9 and Meis1a, two downstream targets of numerous pathways that are deregulated in AML. The results showed evidence of differentiation within two weeks of genetic deinduction of mutant IDH, and two weeks later, six of eight animals showed complete remission with elimination of any detectable leukemic cells. More information at