Posted by rob on December 20, 2005 under Uncategorized | 
WASHINGTON, DC (Dec. 20, 2005) USSoccerPlayers – Everything was going well for Katie Knudson of Portland, Oregon in the spring of 2001. She loved school and her kindergarten teacher and she had a great 6th birthday party. She loved her dance class and was a very cute ballerina. At school, she loved to run and play with her classmates at recess and in P.E. Then school ended and she was out for summer vacation. What could be better than summer vacation when you are six years old?
Then Katie came down with a summer fever. Nothing too serious, but she was lacking her normal energy, and by the next day it was up to 104 degrees. Her parents, Mark and Karen, decided to take her to the doctor just to be safe. The pediatrician, a wonderful woman who had taken care of Katie since she was born, thought it might be a virus that would run its course in a couple of days. Katie’s Mom was still worried and asked the doctor to order some blood work.
On June 22, 2001 the pediatrician called to ask Katie’s parents to take Katie to the hospital immediately. She asked several times during the call, “is Katie okay” and wanted to know “what is she doing right now?” And then, the pediatrician began to cry and through her tears told Katie’s mother, “we think Katie has leukemia.” That day, Katie’s life and the life of her family took a whole new turn.
Katie spent four days in the hospital, having lots of blood drawn, intravenous fluids pumped into her, and her first bone marrow aspiration – a needle inserted into her hip to test the bone marrow. By the time they had Katie’s fever under control and were ready to send her home, they also had a diagnosis – Chronic Myelogenous Leukemia (CML), a type of leukemia usually found in people over 60 that is extremely rare in young children. Katie may have been the youngest person in the United States with CML in 2001.
As soon as Katie was released from the hospital, she began outpatient chemotherapy. The doctors started with a drug intended to help improve her blood quality without all the side effects associated with more aggressive chemotherapy. During 1995-2001 the three to five (3-5) year survival rate for patients diagnosed with CML was less than 40%. The doctors described the treatment plan for CML – chemotherapy, radiation, and Katie would need a bone marrow transplant before Christmas. The doctors explained both the relatively low survival rate of CML patients and the potential for serious adverse lifelong effects as a result of the treatments for even those who survive.
With no choice apparent, the Knudson family began the search for a bone marrow donor. No family member was a match, but the family was incredibly relieved when they found a suitable unrelated donor. Katie and her family met with the doctors and staff at Doernbecher Children’s Hospital, who would be responsible for the bone marrow transplant. The doctors confirmed Mark and Karen’s fears about the serious long-term health problems associated with some bone marrow transplants.
The doctors then discussed another option with the Knudsons – a new drug, “Gleevec” – that had been approved by the United States Food and Drug Administration (“FDA”) only a few weeks earlier. Gleevec was developed by the pharmaceutical company Novartis. When physician and researcher Brian Druker proposed to conduct clinical trials to see if Gleevec might be effective for treating certain forms of leukemia, Novartis was not willing to bear those costs, so Dr. Druker turned to the Leukemia & Lymphoma Society (the “Society”). The Society funded Dr. Druker’s research and the research was successful. CML was precisely the type of cancer that Gleevec treats, but because CML is so rare in young children, fewer than a dozen children had ever been treated with Gleevec.
Katie started taking Gleevec on August 8, 2001. Every evening after dinner she takes two pills. No aggressive chemotherapy with the profound side effects. No hair loss. No hospitalization. No bone marrow transplant. Regular hospital visits, many bone marrow aspirations – the needles inserted into her hip to test the bone marrow, but in six months the Gleevec had worked – Katie’s leukemia was in remission.
Today, four years later, Katie still takes the Gleevec pills. She still has appointments at the pediatric hematology ward for examinations and twice a year they test her bone marrow, but there have been no signs of the leukemia that changed everything so suddenly in 2001. Katie’s leukemia is not “cured” – and it remains a constant concern that a bone marrow transplant or other treatments will be necessary in the future.
Through all the stress and fear the Knudson family endured, Katie has blossomed. Ballet gave way to soccer as Katie’s favorite activity and now she plays softball and golf as well.
Aware of all that the Leukemia & Lymphoma Society’s funding of Dr. Druker’s research has given them, Katie and her family have committed themselves to giving back. Gleevec meant that Katie Knudson never lost her hair, so she donated her beautiful waist-length brown hair to “Locks of Love,” to help someone else who will have to endure the aggressive chemotherapy the Knudsons have avoided. Katie’s story and her parents’ decision to select Gleevec over the potential cure offered by a bone marrow transplant have been discussed in Newsweek and other national publications.
Katie and her family have become leaders in the cancer community. Katie participates in the Leukemia & Lymphoma Society’s annual “Light the Night” fundraising events. Katie has been a spokesperson and poster child for the Society’s “Pennies for Patients” program, which raises over $10 million per year and reaches six million children in 12,000 schools. Katie has been the “honored hero” for several Team in Training events. She has also been a featured “honored hero” for Soccer Kicks for Cancer, the national program for youth soccer players and teams that was launched in 2005 by the US National Soccer Team players along with the Society and the US Youth Soccer Association. Pictures of Katie with US National Team star Landon Donovan appear in the US National Soccer Team Players website and at the Soccer Kicks for Cancer website. Katie’s artwork is part of the 2006 Leukemia & Lymphoma Society “Twelve Months of Hope” calendar.
After Hurricane Katrina hit the Gulf Coast and the Portland Water Bureau sent people and trucks, one of the mechanics going to New Orleans asked for some yellow Lance Armstrong Livestrong bracelets to distribute to people in New Orleans. Katie and her family responded by providing a bag full of Livestrong bracelets and the red Leukemia & Lymphoma Society bracelets with the message “Relentless,” as in “Relentless for a Cure.”
While Katie and her family have become dedicated to the Leukemia & Lymphoma Society and the cancer community, their commitment has not prevented Katie from having fun doing all the things a ten year-old girl should be doing. She loves to play soccer and her coaches love to see her at practice and on the field. She is not the fastest player on her team or the strongest, but she always does her best and gives 100%. For her teammates and their parents, who know what Katie and her family have been through, Katie contributes something extra – inspiration to everyone else and a reminder of how precious and sometimes how fleeting good health can be. No matter how she plays, she has a smile on her face. But, then, she and her family all have good reasons to smile. The US National Soccer Team Players are privileged to be able to welcome Katie Knudson as a Time In program honoree.
Time In – Katie Knudson
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One night in late October, Dr. Deborah Dunsire endured a fitful night’s sleep.
Dunsire, president and CEO of Millennium Pharmaceuticals Inc. for just three months, was hours away from announcing more than 100 layoffs. She would also tell employees Millennium was ending its promising research into inflammation and redirecting its discovery budget solely toward the pursuit of new cancer treatments.
“We had to look at great people who have done terrific work that helped Millennium be where it is and (then) say to them, ‘Unfortunately you won’t be going forward,’ ” Dunsire said. “That dissonance is what keeps you awake.”
Dunsire announced the cutbacks, moving ahead with an aggressive plan to focus the company primarily on cancer drug development and boost sales efforts for its cancer drug Velcade. It’s a mandate she assumed over the summer after succeeding founder and longtime CEO Mark Levin, who launched Millennium in 1993 as a gene researcher that licensed technology to third parties and then, through acquisitions, transformed it into a drug developer.
Her first step toward a new focus for the company took place in July, when Dunsire executed a plan negotiated before her arrival for Millennium (Nasdaq: MLNM) to give up co-promotion rights to Schering-Plough Corp. (NYSE: SGP) for Integrilin, a cardiovascular drug the companies co-developed. Many of Millennium’s 200 Integrilin sales and marketing jobs subsequently moved to Schering-Plough. That and October’s layoffs will bring Millennium’s employment down to about 1,100 from last year’s 1,500.
Dunsire will be tapping into 17 years of experience with Switzerland’s Novartis AG (NYSE: NVS) and its predecessor companies as she hashes out Millennium’s long-term commercial plans.
She most recently ran Novartis’ North American oncology operations and helped engineer domestic launches of a number of drugs, including the cancer treatment Gleevec in 2001, which has surpassed $1 billion in annual global sales.
Jerry Karabelas, an old boss from that period, said Dunsire is the right executive for the job, even in the wake of the departure of the visionary Levin.
“She’s very smart and focused,” said Karabelas, a partner with Care Capital LLC in New Jersey and a former head of Novartis’ health care division. “She can set and articulate a vision, identify key issues, organize and motivate an organization and direct them to solutions.”
Levin, who continues to serve as a Millennium board member, said the company looked at more than 50 candidates over the last three years before identifying Dunsire as a potential new CEO. Dunsire made strong impressions early on, during an initial airport meeting at the Newark Marriott.
“She was passionate right from the beginning about building a company that would make a big difference in people’s lives,” he said. “And she was focused on building a company for the long term.”
Dunsire’s job won’t be easy. Millennium lost $252.3 million in 2004 even as it reduced red ink and boosted product sales. Losses over the first three quarters of this year hit $154 million, driven in part by restructuring charges left over from the layoff of more than 600 people in 2003 in what also represented a major restructuring and initial narrowing of development focus. Millennium boosted revenue to more than $201.6 million in the third quarter by increasing Velcade sales but also because of one-time revenue sources. Still, clinical trials for three cancer compounds and four inflammation treatments that have made it past the discovery stage are either planned or under way.
The South African-born Dunsire, a former physician who speaks in measured academic language from behind wire-rimmed glasses, said she addresses top decisions by working with and seeking feedback from other executives.
“This business is too complex,” she said. “Any person in this type of role who believes they have all the answers and tries to do it alone, I think, is dangerous.”
And she tries to be transparent about her intentions. Dunsire, 43, ran six town hall-style meetings at Millennium’s headquarters so employees could ask questions about the restructuring. That approach, she said, reflects her overall goals of being quick, honest and clear about her plans.
“I really do believe that when you do something you need to do it well,” she said. “And I absolutely believe if we had tried to continue to do both inflammation and oncology we would have at best been mediocre, and then the whole company suffers.”
Some congratulated the action as necessary for Millennium to achieve its goal of pro forma operating profitability next year.
“She’s doing the right things,” said Christopher Raymond, a Chicago-based analyst with Robert W. Baird & Co.
Dunsire, who now lives in Weston, often works 60 to 70 hours per week, but she also takes time for family, taking road trips with her husband and two children or going swimming and doing “the soccer mom thing.” Dunsire loves orchids (“They are kind of peaceful,” she said) and three grow in her lime-green office. Pictures of her children sit right by her desk, and large modern bookcases display photos from charity events featuring both sides of the political spectrum. At least one includes Dunsire with former President George H.W. Bush and First Lady Barbara Bush. Another photo features Dunsire with Bush’s successor, Bill Clinton, and Sen. Hillary Clinton.
One photo hangs prominently on a side wall: A picture of 50 Gleevec patients celebrating the drug’s launch, all of whom survived because of the medicine she helped launch commercially.
“That’s the reward, really,” she said.
Mark Hollmer can be reached at mhollmer@bizjournals.com.
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A fresh look at the delicate dance of enzymes within living cells has provided insights into how one genetic mutation can lead to three distinct blood disorders.
The discovery ?provides new and important insights into how this gene contributes to the development of myeloproliferative disease,? said D. Gary Gilliland, a Howard Hughes Medical Institute researcher at Brigham and Women’s Hospital and Harvard Medical School. ?It should provide an important foundation for subsequent development of new drugs,? he added.
?Although relatively rare individually, together these disorders are about five times more common than chronic myelogenous leukemia.?
D. Gary Gilliland
The new research results, found in collaboration with biologist Harvey Lodish’s team at the Whitehead Institute for Biomedical Research, were announced December 19, 2005, in an immediate early online publication in the Proceedings of the National Academy of Sciences.
What the teams of scientists are trying to decipher is the molecular explanation for how the protein encoded by this single gene – called JAK2V617F – can be the culprit in three different leukemia-like diseases. They want to know how and why the protein produced by this gene cooperates with other signaling proteins to touch off disease.
The three leukemia-related disorders caused by the mutation are each characterized by abnormal growth of blood system cells. The first, polycythemia vera, involves ultra-high red blood cell counts. The second, essential thrombocythemia, results from excess growth of blood platelets. And the third, myelofibrosis with myeloid metaplasia, stems from abnormal growth of fibroblast cells, making the bone marrow abnormally dense.
Patients who have these disorders are generally older, and there are about 100,000 in the United States. At present, patients with any of the three disorders receive empirically derived drug treatments similar to those used that used to be used to treat chronic myelogenous leukemia (CML).
The three blood disorders can all become dangerous forms of adult leukemia. ?They are technically cancers in their own right,? Gilliland explained. They tend to be slow-growing, and they are sometimes detected before severe symptoms arise, as is true with CML. Although relatively rare individually, together these disorders are about five times more common than CML, Gilliland said.
The research teams hope their findings will help them develop targeted drug therapies for the three disorders, similar to what has already been achieved for CML with the drug Gleevec.
In earlier work, Gilliland and three other teams of investigators found that the damaging mutation in the gene for JAK2V617F occurs later in life – and is acquired rather than inherited. It is not yet known why this single gene mutation causes different disorders in different patients, but it does show that those disorders have much in common. Other, more aggressive leukemias are known to result from different kinds of genetic damage, such as gene rearrangements caused by chromosome breakage.
The two research teams at Harvard and the Whitehead Institute studied the mutation, which occurs in a gene that makes an enzyme called a kinase. This particular kinase is one link in a chain – a kinase cascade ? that sends a signal from the cell surface to the nucleus, spurring a reaction such as cell division.
The kinase is normally pressed into action by the arrival of a molecule that docks with a specific receptor sitting on the cell’s surface. Arrival of the outside signal, like guests ringing a doorbell, sets off a cascade of events inside the cell. The kinase’s job, once the doorbell is rung, is to add a phosphate group to another protein. This sends a message that eventually reaches the nucleus and sets off some action, such as cell division.
The problem is that a strategic mutation can change everything. In these three blood disorders, for example, the mutant gene makes an abnormal kinase, like a faulty doorbell that won’t shut off, and the kinase constantly transmits a signal down the chain of command, whether it’s needed or not. The signal thus spurs abnormal activity – and too much growth causes overgrowth of a particular type of blood cell, leading to leukemia.
The researchers demonstrated that the faulty kinase can only trigger this excessive growth in cells that have its corresponding receptor. Since this receptor is found only in certain types of blood cells, their work helps explain why a mutation in JAK2V617F can trigger three distinct blood disorders – but has not been found to be associated with disorders originating in other types of blood cells.
Although more research is needed, ?these studies advance our understanding of the basis of myeloproliferative diseases,? Gilliland said. ?Ultimately it’s going to lead to curative strategies – we hope.?
HHMI News: Researchers Closer to Understanding How One Mutation Causes Three Different Blood Disorders
