Posted by rob on February 28, 2005 under Uncategorized | 
NCCN Releases Acute Myeloid Leukemia and Chronic Myelogenous Leukemia Chapters of the NCCN Drugs & Biologics Compendium
BIOWIRE2K
JENKINTOWN, Pa.–(BUSINESS WIRE)–Feb. 28, 2005–The National Comprehensive Cancer Network (NCCN) announces the release of Chapters 4 and 5 of the NCCN Drugs & Biologics Compendium(TM): Acute Myeloid Leukemia and Chronic Myelogenous Leukemia.
“The NCCN Drugs & Biologics Compendium contains authoritative and definitive information about the appropriate use of drugs and biologics in the care of patients with leukemia – information that decision-makers at insurance and managed care companies and pharmacy benefits managers can use to establish coverage policy,” said William T. McGivney, Ph.D., CEO of the NCCN. “With the release of the leukemia chapters, NCCN utilization information adds to a long list of scientific, evaluative products to facilitate decision-making about appropriate cancer care.”
The NCCN Drugs & Biologics Compendium outlines the appropriate uses of drugs and biologics in the care of cancer patients, as derived from the NCCN Clinical Practice Guidelines in Oncology(TM) — recognized and applied nationally as the standard for clinical policy in oncology. Listed uses include FDA-approved indications as well as those beyond FDA labeling. As with the guidelines, the Compendium spans the continuum of cancer care from early stage to advanced stage disease, and from supportive to palliative care.
Oncology care professionals can visit www.nccn.org to access the most up-to-date version of the NCCN Drugs & Biologics Compendium online or to request a free printed copy.
For more information on the NCCN Drugs & Biologics Compendium and other NCCN programs, please contact NCCN at 215-690-0254 or at www.nccn.org.
The National Comprehensive Cancer Network (NCCN), an alliance of 19 of the world’s leading cancer centers, is an authoritative source of information to help patients and health professionals make informed decisions about cancer care. Through the collective expertise of its member institutions, the NCCN develops, updates, and disseminates a complete library of clinical practice guidelines. These guidelines are the standard for clinical policy in oncology. NCCN’s complete spectrum of programs emphasizes improving the quality, effectiveness, and efficiency of oncology practice. Programs include: Clinical Practice Guidelines in Oncology(TM), Drugs & Biologics Compendium(TM), Treatment Guidelines for Patients, the Journal of the National Comprehensive Cancer Network, Leukemia Resource Line, educational conferences and symposia for clinicians, Oncology Outcomes Project, Clinical Trials Network, Cancer Case Manager, and collaborations with managed care organizations.
NCCN member institutions include:
– City of Hope Cancer Center
– Dana-Farber/Partners CancerCare
– Duke Comprehensive Cancer Center
– Fox Chase Cancer Center
– Huntsman Cancer Institute at the University of Utah
– Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
– Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University
– The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
– Robert H. Lurie Comprehensive Cancer Center of Northwestern University
– Memorial Sloan-Kettering Cancer Center
– H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida
– Roswell Park Cancer Institute
– St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute
– Stanford Hospital & Clinics
– University of Alabama at Birmingham Comprehensive Cancer Center
– UCSF Comprehensive Cancer Center
– University of Michigan Comprehensive Cancer Center
– UNMC Eppley Cancer Center at The Nebraska Medical Center
– The University of Texas M.D. Anderson Cancer Center
For more information, visit www.nccn.org.
NCCN Releases Acute Myeloid Leukemia and Chronic Myelogenous Leukemia Chapters of the NCCN Drugs & Biologics Compendium
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By Linda McCartyThe Winchester Star
If life starts to get her down, Susan Schabos pick-me-up is her 22-year-old son, Tommy Cleaver.
Hes really had a lot to overcome, and he gives me strength and a positive outlook on life, said Schabo, who lives in Winchester.
Susan Schabo of Winchester said she is inspired by her sons ability to excel in football and continue on with his college studies while he had undergone treament for chronic myelogenous leukemia. (Photos by Ginger Perry)Cleaver, a Maryland resident, was studying and playing football at Middlebury College in Vermont in 2001, when he was diagnosed with chronic myelogenous leukemia, a bone-marrow cancer.
I was playing football in the fall of 2001 and had a hemorrhage in my right eye, Cleaver said recently, while visiting his mother, sister, Amber Schabo, 14, and brother, Joshua Schabo, 13.
Following extensive tests, doctors discovered that Cleavers white blood cell count was extremely high.
They did a bone marrow biopsy, Cleaver said, and diagnosed CNL.
Cleaver said he was in shock when he heard the diagnosis.
But I didnt dwell on it too much, he said. I just had a lot of faith.
Schabo was home when she received word of her sons illness.
When I got up there, I was falling apart, and he was holding me together, Schabo said. He comforted me.
Cleaver was transferred for treatment from a hospital in Vermont to Johns Hopkins Medical Center in Baltimore. He had a round of chemotherapy and then was put on an experimental drug, Gleevec.
Ive been in remission for three years today, Cleaver said on Feb. 14. Theres no cure, but hopefully, Ill stay in remission.
Cleaver missed that semester in school, but returned during the spring of 2002 and began playing football again that year.
My doctor wasnt really thrilled that I played football, but I had my blood checked weekly during the season to make sure it was OK, he said, and it was.
Football helped Cleaver to cope with his illness, he said. It was my release from the situation.
As a result, he excelled as a player. By the time Cleaver graduated in January, he was his schools leading receiver and had earned records for most catches during a game and season and most yards receiving during a game, season, and career.
During Cleavers junior and senior years, he was first-team, all-conference selection, and during his senior year he was a first-team, All New England selection.
In December, Cleaver was one of 15 student athletes to be named a 2004 National Scholar Athlete by the National Football Foundation and the College Hall of Fame.
Right now, Cleaver is looking for a job in either investment banking or commercial real estate and wants to live in Baltimore, Washington, D.C., or possibly New York City.
Although Cleavers disease isnt curable, he doesnt dwell on the possibility that it may reoccur again.
I dont see how worrying would help, he said. Im a firm believer that everything happens for a reason. I want to learn from this and grow as a result. If I come out of remission, I will cross that road when I get there.
Tommy has truly taught me not to give up, and to have faith, Schabo said. He is my inspiration.
Link: http://www.winchesterstar.com/TheWinchesterStar/050228/Area_illness.asp
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New Drug May Be Formidable Adversary For Hard To Treat Leukemia
As scientists uncover the precise molecular mechanisms that underlie effective cancer treatments, they gain invaluable insight into why predominantly successful treatments fail for some patients. A new study published in the February issue of Cancer Cell reveals how detailed information about the action of an existing drug was used to design a compound that is effective against some notoriously treatment resistant cancer cases.
Despite the resounding success of anticancer drug imatinib (Gleevec) as a treatment of chronic myeloid leukemia (CML), a small but growing number of patients develop resistance to the drug and relapse. Imatinib inhibits the activity of Bcr-Abl, a protein that is abnormally active in most CML patients. Relapse and resistance to imatinib in patients with advanced disease is linked to the emergence of additional mutant forms of Bcr-Abl that are not inhibited by imatinib.
A group led by Dr. James D. Griffin from the Dana-Farber Cancer Institute working with scientists at Novartis Pharma AG in Switzerland used data obtained from structural examination of the molecular interaction between imatinib and Abl to design AMN107, a compound that has a stronger and more complete molecular association with Abl. AMN107 effectively blocked proliferation of Bcr-Abl dependent cells derived from CML patients and was an even more potent inhibitor of Bcr-Abl than imatinib. Importantly, AMN107 inhibited the growth of cells expressing many Bcr-Abl mutants that were resistant to imatinib and oral administration of AMN107 prolonged survival in imatinib-resistant CML mouse models.
Phase I clinical trials with AMN107 have just started. “If human clinical trials validate the effectiveness of AMN107 demonstrated in the preclinical studies reported here, it may be possible to either use AMN107 in selected patients with imatinib resistance, or to use both agents together, simultaneously or sequentially,” says Dr. Griffin. The researchers are hopeful that combined therapy may suppress emergence of treatment resistant Abl mutants and that availability of novel, high potency, Abl tyrosine kinase inhibitors will usher in a new generation of clinical studies that may result in additional major advances in the therapy of hard to treat leukemia.
###
Ellen Weisberg, Paul W. Manley, Werner Breitenstein, Josef Brüggen, Sandra W. Cowan-Jacob, Arghya Ray, Brian Huntly, Doriano Fabbro, Gabriele Fendrich, Elizabeth Hall-Meyers, Andrew L. Kung, Jürgen Mestan, George Q. Daley, Linda Callahan, Laurie Catley, Cara Cavazza, Azam Mohammed, Donna Neuberg, Renee D. Wright, D. Gary Gilliland, and James D. Griffin: “Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl”
The researchers included Ellen Weisberg, Arghya Ray, Elizabeth Hall-Meyers, Linda Callahan, Laurie Catley, Cara Cavazza, Donna Neuberg, and James D. Griffin of Dana-Farber Cancer Institute in Boston; Paul W. Manley, Werner Breitenstein, Josef Brüggen, Sandra W. Cowan-Jacob, Doriano Fabbro, Gabriele Fendrich, and Jürgen Mestan of Novartis Institutes for Biomedical Research in Basel; Brian Huntly, Renee D. Wright, and D. Gary Gilliland of Brigham and Women’s Hospital in Boston; Andrew L. Kung of Dana-Farber Cancer Institute and Children’s Hospital in Boston; and George Q. Daley and Azam Mohammed of Children’s Hospital in Boston. This research was supported by NIH grants, a Specialized Center of Research Award from the Leukemia and Lymphoma Society, grants from the National Cancer Institute, the NIH Director’s Pioneer Award and the Burroughs Wellcome Fund. P.W.M., W.B., J.B., S.W.C.-J., D.F., G.F., and J.M. are employees of Novartis Pharma AG, Basel, Switzerland. J.D.G has a financial interest with Novartis Pharma AG.
Publishing in Cancer Cell, Volume 7, Number 2, February 2005, pages 129-141. http://www.cancercell.org/
This story has been adapted from a news release issued by Cell Press.
URL: http://www.sciencedaily.com/releases/2005/02/050218131439.htm
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Pope John Paul II, flanked by Vatican Secretary of State cardinal Angelo Sodano, waves to the small crowd from behind a window at Rome’s Gemelli Polyclinic Hospital, Sunday.
Posted by rob on under Uncategorized |
A newborn zebra stands with his mother.
Posted by rob on February 27, 2005 under Uncategorized |
A Russian model presents hair design ‘Wedding’ at a show at the St.Petersburg international contest
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CHS senior battling leukemia
When Brittany Randle’s knees started aching during the first week of soccer practice earlier this month, she scheduled an appointment with her family physician.
“I couldn’t even get up in the mornings,” Randle said.
The popular Ceres High senior was diagnosed with leukemia on Thursday.
“If anybody can fight this thing and be successful, it’s Brittany Randle,” said Ceres High varsity girls soccer coach Randy Cerny. “She has strong faith.”
Added Randle: “A lot of people are taking it worse than I am. I just have to get it treated.”
Randle watched the Ceres High varsity girls basketball team compete against the Davis Spartans in Ceres Thursday night. She was greeted with hugs from students and administrators, including Ceres High principal Bob Palous.
“Everybody is rallying around her,” Cerny said.
Said Randle: “It’s just nice to know I have a lot of support.”
Randle has chronic myelogenous leukemia (CML). The diagnosis was made after a specialist in Modesto examined her blood and marrow cell.
About 4,600 new cases of CML are diagnosed each year in the United States. CML results from an acquired (not inherited) injury to the DNA of a stem cell in the marrow. The result of this injury is the uncontrolled growth of white cells leading, if unchecked, to a massive increase in their concentration in the blood.
“The average person has 4,000 to 13,000 white cells,” Randle said. “I had 109,000.”
Randle started treatment the day she was diagnosed. She was prescribed an oral medication. Randle takes a pill four times a day.
“If the pills don’t work, I’m going to have to get a bone marrow transplant,” she said.
On Monday morning, Randle visited her teammates at practice at Walter White School.
“She’s going to continue to be a part of this team,” Cerny said. “In what capacity, I don’t know. If she could even step on the field for one minute, she would.”
Randle played in just about every game for the varsity Bulldogs the last three years. As a starter on defense, Randle earned second-team, all-Central California Conference honors as a sophomore and was an honorable-mention selection as a junior.
The Bulldogs will miss Randle’s leadership on the field.
“It’s hard,” Randle said. “This is the time I’m supposed to be training the hardest for college. That’s the worse part of it. I can’t play.”
Added Cerny: “We don’t have anybody at our school that can replace that girl. She has some great ability.
“She leads by example. She goes out and plays hard and it brings up the level of play for the girls that are around her.”
Cerny and Randle have a great relationship off the field.
She’s been babysitting for his family the last four years.
“Brittany Randle is a top-quality person,” Cerny said. “She’s honorable. She’s ethical. She’s intelligent. She’s athletic. She has a great sense of humor. She’s a very friendly person. I love that kid.”
The Leukemia & Lymphoma Society contributed to this report. – By DALE BUTLER /
Archives: Story
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Study finds mechanism for drug resistence
Source: (cancerfacts.com)
Friday, February 25, 2005
BOSTON – Feb. 25, 2005 – A new study shows that a second mutation in a gene associated with non-small-cell lung cancer (NSCLC) helps to explain how the tumors become resistant to new generation drugs like gefitinib (Iressa®).
Led by Dr. Balazs Halmos, a physician-scientist formerly at Beth Israel Deaconess Medical Center and now with the University Hospitals of Cleveland, and Dr. Daniel Tenen, a molecular biologist at Beth Israel, the researchers found that the non-small cell lung tumors appear to develop a second mutation that allows them to evade the action of the new generation drugs.
“The development of a second mutation suggests that the tumor cells remain dependent on an active EGFR pathway for their proliferation,” Tenen said in a prepared statement. “This mirrors the situation that developed over the past few years among patients with chronic myeloid leukemia and gastrointestinal stromal tumors who were being treated with imatinib (Gleevec®).”
The new drugs are designed to target a specific gene mutation that produces an abnormal epidermal growth factor protein (EGFR), which allows the tumor to grow unchecked. Gleevec is a similarly designed drug that has been very effective in the treatment of a certain type of leukemia. In some people, however, Gleevec seems to gradually lose effectiveness.
In those cases, says Tenen, who is also a professor of medicine at Harvard Medical School, the identification of mechanisms of resistance helped lead to the development of second-generation inhibitor drugs. The new study appears in the Feb. 24, 2005 issue of The New England Journal of Medicine.
Gefitinib is one of a new generation of cancer drugs that work by disrupting a specific molecular target within the cell. In this case the abnormal protein responsible for stimulating tumor growth. Gefitinib acts on the receptor for the epidermal growth factor protein (EGFR) to halt the proliferation of cancer cells. In 2003, it was approved by the U.S. FDA as a treatment for non-small cell lung cancer.
Clinical applications of the new drug initially yielded very encouraging results, with approximately 10 percent of patients experiencing complete remissions. Unfortunately, the remissions were not long-lived and the cancer returned.
Hypothesizing that the relapses may have been due to another mutation in the EGFR gene that was causing cancer cells to become resistant to the drug, the researchers obtained a second tissue sample of the tumor from patients treated with gefitinib and resequenced, or remapped, the genetic sequence of the EGFR gene.
Their studies confirmed the existence of a second mutation, and insertion of this mutation into cells in test tubes made them resistant to gefitinib. Further analysis showed that the newly identified mutation was altering gefitinib’s binding pocket and thereby changing the “keyhole” so that the “key” in gefitinib no longer fit.
According to study coauthor Dr. Bruce Johnson, director of the Dana-Farber/Harvard Cancer Center Lung Program, clinical investigators are already moving to develop a new drug designed to overcome this second mutation.
“Our preliminary results have yielded encouraging findings, pointing towards drugs that might bypass this method of resistance,” says Johnson. “We’re now in the process of planning clinical studies to test novel EGFR inhibitor compounds in lung-cancer patients whose tumors have become resistant to gefitinib.”
cancerfacts.com.
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Improved outcome in HLA-identical sibling hematopoietic stem cell transplantation for acute myelogenous leukemia (AML) predicted by KIR and HLA genotypes.
Hsu KC, Keever-Taylor CA, Wilton A, Pinto C, Heller G, Arkun K, O’reilly RJ, Horowitz MM, Dupont B
Blood. 2005 Feb 24;
Inhibitory killer Ig-like receptors (KIR) recognize HLA-C and -B epitopes on target cells, thereby regulating natural killer (NK) cell activity. In 178 patients receiving T-cell depleted HLA-identical sibling transplants for CML, ALL, AML, and MDS, analysis of donor KIR genotype with HLA genotype demonstrated that 62.9% of the patients lacked an HLA ligand for donor inhibitory KIR. Lack of HLA ligand for donor inhibitory KIR (“missing KIR ligand”) had no effect on disease-free survival (DFS), overall survival (OS), or relapse in patients receiving transplants for CML and ALL. There was, however, a significant missing KIR ligand effect in AML and MDS on DFS (p=0.014, HR 0.53, 95% CI 0.28-0.88) and OS (p=0.03, HR 0.53, 95% CI 0.3-0.93). Incidence of relapse was also lower in AML and MDS patients lacking HLA ligand for donor inhibitory KIR (p=0.04, HR 0.41, 95% CI 0.18-0.97). AML and MDS patients lacking two HLA ligands for donor inhibitory KIR had the highest DFS (p=0.002) and OS (p=0.003). There was no significant contribution of donor activating KIR to transplant outcome in these patients. These data indicate that absence of class I ligand in the recipient for donor inhibitory KIR can be a prognostic factor for transplant outcome in HLA-identical sibling transplants, and that lack of either HLA-C or -B ligands for donor inhibitory KIR can contribute to improved outcome in AML and MDS.
Improved outcome in HLA-identical sibling hematopoietic stem cell transplantation for acute myelogenous leukemia (AML) predicted by KIR and HLA genotypes.
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[Experimental study of K562 cell apoptosis induced by siRNA.]
Chen BB, Fan HH, Lin GW, Yuan ZH, Lu HZ, Gao L, Liu Y
Zhonghua Xue Ye Xue Za Zhi. 2004 Dec ; 25(12): 717-9
OBJECTIVES: To construct a siRNA expression vector pBCR6 that produces siRNA against bcr/abl mRNA and detect apoptosis rate of K562 cells after pBCR6 transfection. METHODS: Template sequence for siRNA was designed, synthesized and inserted into an expression vector pSilencer1.0-U6. Restriction analysis and sequencing were performed to verify the pBCR6 vector. Then pBCR6 was transfected into K562 cells by X-tremeGene Q2. pSilencer1.0-U6 was used as the control. At different time point after transfection, apoptosis rate was determined by Tunel and Annexin V+ PI with FCM. RESULT: pBCR6 was verified by restriction analysis and sequencing. The apoptosis rate of K562 cells markedly increased at 48 and 72 hour after transfected with pBCR6, and increased in a time-dependent manner [the apoptosis rate of transfected K562 cells was (47.80 +/- 1.63)% at 72 hrs, wheras the control group was (6.67 +/- 0.37)%, P
[Experimental study of K562 cell apoptosis induced by siRNA.]
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Pharmacogenomics and the Drug Discovery Pipeline : When Should it Be Implemented?
Penny MA, McHale D
Am J Pharmacogenomics. 2005; 5(1): 53-62
One of the key factors in developing improved medicines lies in understanding the molecular basis of the complex diseases we treat. Investigation of genetic associations with disease utilizing advances in linkage disequilibrium-based whole genome association strategies will provide novel targets for therapy and define relevant pathways contributing to disease pathogenesis. Genetic studies in conjunction with gene expression, proteomic, and metabonomic analyses provide a powerful tool to identify molecular subtypes of disease. Using these molecular data, pharmacogenomics has the potential to impact on the drug discovery and development process at many stages of the pipeline, contributing to both target identification and increased confidence in the therapeutic rationale. This is exemplified by the identified association of 5-lipoxygenase-activating protein (ALOX5AP/FLAP) with increased risk of myocardial infarction, and of the chemokine receptor 5 (CCR5) with HIV infection and therapy. Pharmacogenomics has already been used in oncology to demonstrate that molecular data facilitates assessment of disease heterogeneity, and thus identification of molecular markers of response to drugs such as imatinib mesylate (Gleevec((R))) and trastuzumab (Herceptin((R))).Knowledge of genetic variation in a target allows early assessment of the clinical significance of polymorphism through the appropriate design of preclinical studies and use of relevant animal models. A focussed pharmacogenomic strategy at the preclinical phase of drug development will produce data to inform the pharmacogenomic plan for exploratory and full development of compounds. Opportunities post-approval show the value of large well-characterized data sets for a systematic assessment of the contribution of genetic determinants to adverse drug reactions and efficacy. The availability of genomic samples in large phase IV trials also provides a valuable resource for further understanding the molecular basis of disease heterogeneity, providing data that feeds back into the drug discovery process in target identification and validation for the next generation of improved medicines.
Pharmacogenomics and the Drug Discovery Pipeline : When Should it Be Implemented?
Posted by rob on February 26, 2005 under Uncategorized |
St. Peter’s dome is silhouetted against the sunset
Posted by rob on February 25, 2005 under Uncategorized |
A man climbs the stairs of the Lincoln Memorial during a snow storm in Washington, DC.
Posted by rob on February 24, 2005 under Uncategorized |
[New approach in the diagnosis and monitoring of treatment of chronic myelogenous leukemia]
Matolcsy A
Orv Hetil. 2004 Dec 26; 145(52): 2603-9
The chronic myelogenous leukemia is a pluripotent hemopoetic stem cell disease characterized by the t(9;22) (q34;q11) reciprocal chromosomal translocation (Philadelphia chromosome). The translocation result the fusion of the ABL gene located at the long arm of chromosome 9 with the BCR gene located at the long arm of chromosome 22. The BCR/ABL fusion gene encodes a chimeric protein with elevated tyrosine kinase activity, that plays an important role in the pathogenesis of the disease. In the diagnosis of chronic myelogenous leukemia and in the evaluation of the therapeutic effect, the detection of the t(9;22)(q34;q11) translocation and BCR/ABL fusion gene plays an important role. The authors in the present paper provides a review on the recently used methods of the detection of t(9;22)(q34;q11) chromosomal translocation and BCR/ABL fusion gene and their role in the diagnosis, monitoring and evaluation of therapeutic effect in chronic myelogenous leukemia.
[New approach in the diagnosis and monitoring of treatment of chronic myelogenous leukemia]
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Pleural-pericardic effusion as uncommon complication in CML patients treated with Imatinib.
Breccia M, D’Elia GM, D’Andrea M, Latagliata R, Alimena G
Eur J Haematol. 2005 Jan ; 74(1): 89-90
Pleural-pericardic effusion as uncommon complication in CML patients treated with Imatinib.
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A South Korean boy spins a fireball in southern Seoul as part of celebrations marking the year’s first full moon day, which has been widely observed in China and other Asian countries.
Posted by rob on February 23, 2005 under Uncategorized |
Cytogenetic testing for therapeutic indication in cancer.
Mundle S, Noskina Y
Expert Rev Mol Diagn. 2005 Jan ; 5(1): 23-9
The association of cytogenetic abnormalities with cancer is well established. However, due to the historic lack of specific insight into the functional role of these anomalies, they have mostly served as diagnostic and/or prognostic indicators. Recent developments in chronic myelogenous leukemia and breast cancer have raised hopes for specific cytogenetic alterations to serve as therapeutic targets. This article reviews the aid provided by molecular diagnostics in these exciting developments in the cancer arena.
Cytogenetic testing for therapeutic indication in cancer.
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Mastocytosis: pathology, genetics, and current options for therapy.
Valent P, Akin C, Sperr WR, Mayerhofer M, Födinger M, Fritsche-Polanz R, Sotlar K, Escribano L, Arock M, Horny HP, Metcalfe DD
Leuk Lymphoma. 2005 Jan ; 46(1): 35-48
Mast cell disorders are defined by an abnormal accumulation of tissue mast cells (MCs) in one or more organ systems. Symptoms in mastocytosis result from MC-derived mediators and, less frequently, from destructive infiltration of MCs. Cutaneous mastocytosis (CM) is a benign disease of the skin and may regress spontaneously. Systemic mastocytosis (SM) is a persistent disease in which a somatic c-kit mutation at codon 816 is usually detectable in MCs and their progenitors. The clinical course in these patients is variable ranging from asymptomatic for years to highly aggressive and rapidly devastating. The WHO discriminates five categories of SM: indolent SM (ISM), aggressive SM (ASM), SM with associated clonal hematological non-MC-lineage disease (AHNMD), and mast cell leukemia (MCL). The c-kit mutation D816V is quite common and may be found in all SM-categories. In SM-AHNMD, additional genetic abnormalities have been reported, whereas no additional defects are yet known for ASM or MCL. Patients with ISM and CM are treated with “mediator-targeting” drugs, whereas patients with ASM or MCL are candidates for cytoreductive therapy. The use of “Kit-targeting” tyrosine kinase inhibitors such as STI571 (Imatinib, Gleevec), has also been suggested. However, the D816V mutation of c-kit is associated with relative resistance against STI571. Therefore, these patients require alternative targeted drugs or new drug-combinations. In patients with SM-AHNMD, separate treatment plans for the SM-component and the AHNMD should be established. Examples include the use of STI571 in patients with SM plus hypereosinophilic syndrome (SM-HES) and the FIPL1/PDGFRA fusion gene target, or chemotherapy for eradication of AML in patients with SM-AML.
Mastocytosis: pathology, genetics, and current options for therapy.
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In the Deep South we have started getting the first flowers of Spring a month earlier than last year.
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Vaccine development for chronic myelogenous leukaemia.
Wong KK, Chatterjee S
Lancet. 2005 Feb 19; 365(9460): 631-2
Vaccine development for chronic myelogenous leukaemia.
