Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response

Posted by rob on August 24, 2004 under Uncategorized | Be the First to Comment

Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response.
Bone Marrow Transplant. 2004 Aug 23; ():
Summary:The immune system of females is capable of recognizing and reacting against the male-specific minor histocompatibility antigen (mHA), HY. Thus, cytotoxic T-lymphocytes (CTLs) recognizing this antigen may be useful in eradicating leukemic cells of a male patient if they can be generated in vivo or in vitro from a human leukocyte antigen (HLA)-identical female donor. The HLA-A(*)0201-restricted HY antigen, FIDSYICQV, is a male-specific mHA. Using HLA-A2/HY peptide tetrameric complexes, we reveal a close association between the emergence of HY peptide-specific CD8(+) T cells in peripheral blood and molecular remission of relapsed BCR/ABL(+) chronic myelogenous leukemia in lymphoid blast crisis in a patient who underwent female-to-male transplantation. Assessment of intracellular cytokine levels identified T cells that produce interferon-gamma in response to the HY peptide during the presence of HY tetramer-positive T cells. These results indicate that transplant with allogeneic HY-specific CTLs has therapeutic potential for relapsed leukemia, and that expansion of such T cells may be involved in the development of a graft-versus-leukemia response against lymphoblastic leukemia cells.Bone Marrow Transplantation advance online publication, 23 August 2004; doi:10.1038/sj.bmt.1704583

http://www.hubmed.org/display.cgi?issn=02683369&uids=15322566

Myeloid/natural killer cell blast crisis representing an additional translocation

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Myeloid/natural killer cell blast crisis representing an additional translocation, t(3;7)(q26;q21) in Philadelphia-positive chronic myelogenous leukemia.
Ann Hematol. 2004 Aug 18; ():
We encountered a patient in blast crisis (BC) with chronic myelogenous leukemia (CML) who showed immunophenotypic features similar to those previously described in acute myeloid/natural killer (NK) cell precursor leukemia. The blasts were positive for CD7, CD33, CD34, and CD56. Cytogenetic analysis disclosed a Philadelphia chromosome (Ph) and t(3;7)(q26;q21). Molecular analysis did not detect any EVI1/CDK6 chimeric transcript generated by t(3;7)(q26;q21), but did indicate overexpression of EVI1, which occurs frequently in progression to myeloid BC in CML. Three cases of myeloid/NK cell precursor BC in CML have been reported, but this case is the first to present with Ph and EVI1 abnormality. These observations suggested that a myeloid/NK cell precursor might have been involved in the Ph-positive clone and have been a target for blastic transformation of CML, although EVI1 expression is not specific for transformation to BC from myeloid/NK lineage.

http://www.hubmed.org/display.cgi?issn=09395555&uids=15322764

Pic Of The Day

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A helicopter is silhouetted against high passing clouds lit up by the setting sun west of Las Vegas, Nevada

Pic Of The Day

Posted by rob on August 23, 2004 under Uncategorized | Be the First to Comment

Two girls fish in the Charles River along the Espalanade in Boston

Pic Of The Day

Posted by rob on August 22, 2004 under Uncategorized | Be the First to Comment

A crowd at a beachside bar in Zouberi, Greece, 20 miles east of central Athens, watch Greek weightlifter Pyrros Dimas as he attempts a lift in the clean and jerk during the Men’s 187 lb (85 kg) event at the Summer Olympics

Pic Of The Day

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Pilgrims with backpacks stand in front of the Cathedral of Santiago de Compostela in northern Spain August 16, 2004. Catholics believe Santiago de Compostela to be the burial place of the Apostle Saint James, whose shrine has drawn pilgrims from all over Europe for more than 1,000 years.

 

Pic Of The Day

Posted by rob on August 20, 2004 under Uncategorized | Be the First to Comment

A young Tibetan girl walks down the steps of a store with a sign in Chinese characters selling food and drinks at Basongcuo Lake in Nyingchi region in southeastern Tibet.

Mayor diagnosed with CML

Posted by rob on August 19, 2004 under Uncategorized | Be the First to Comment

CHATHAM – Chatham Borough Mayor Richard Plambeck said this week that he has been diagnosed with a chronic form of leukemia called chronic myelogenous leukemia or CML. The mayor said he is undergoing chemotherapy.

Plambeck, who was sworn in this year to a four-year term as mayor, said he was diagnosed two weeks ago. He said the diagnosis would not present a conflict with his mayoral duties.

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“I’m feeling fine,” the mayor said this week.

Plambeck said he first became aware that something was wrong when he lost five pounds. But he voiced confidence in his doctors and the treatment he is now undergoing.

Mostly, he said, “I have a good supporting family.”

According to the U.S. National Library of Medicine, CML is “a malignant cancer of the bone marrow that causes rapid growth of the blood forming cells (known as myeloid precursors) in the bone marrow, peripheral blood, and body tissues.”

CML, according to the Library of Medicine, accounts for 7-20 percent cases of leukemia.

“The vast majority of people treated for cancer with radiation do not go on to develop leukemia and it takes many years to develop leukemia from this cause,” according to the Library of Medicine.

“If people notice me drinking a lot of water, this is the reason,” said the mayor.

Thursday, August 19, 2004

http://www.zwire.com/site/news.cfm?newsid=12734151&BRD=1918&PAG=461&dept_id=506415&rfi=6

Detection of BCR/ABL Fusion Product in Normoblasts in a Case of Chronic Myelogenous Leukemia

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Detection of BCR/ABL Fusion Product in Normoblasts in a Case of Chronic Myelogenous Leukemia.
Am J Surg Pathol. 2004 Sep ; 28(9): 1240-4
Erythroblast phase of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute erythroid leukemia are rare events. The distinction between these two entities is poorly defined. The World Health Organization (WHO) classification requires the presence of more than 50% of erythroblasts in the bone marrow for the diagnosis of both the erythroid/myeloid or pure erythroid subtypes of acute erythroid leukemia. However, in previous studies of erythroblast crisis CML, the percentage of erythroid series in the bone marrow is seldom mentioned and the direct relationship of the erythroblasts and the Philadelphia chromosome has never been established. We report a well-documented case of acute erythroid leukemia transformed from CML. The studies in morphology, immunohistochemistry, and flow cytometry fulfill the WHO criteria for the diagnosis of acute erythroid leukemia, and yet the complex karyotype containing Philadelphia chromosome indicates genetic evolution. Finally, the direct demonstration of the BCR/ABL fusion product by fluorescence in situ hybridization in the erythroblasts provides concrete evidence that the erythroblasts are part of the leukemic process and not an innocent bystander.

http://www.hubmed.org/display.cgi?issn=01475185&uids=15316326

Does Benzene Cause Childhood Leukemia?

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Preliminary research suggests that benzene emissions from gas stations and auto repair shops may quadruple the risk of leukemia in children.

http://story.news.yahoo.com/news?tmpl=story&cid=97&ncid=751&e=11&u=/hsn/20040819/hl_hsn/doesbenzenecausechildhoodleukemia

Disease-related potential of mutations

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Disease-related potential of mutations in transcriptional cofactors CREB-binding protein and p300 in leukemias.
Cancer Lett. 2004 Sep 15; 213(1): 11-20
CREB-binding protein (CBP) and highly related p300 protein are transcriptional co-activators that play an essential role in chromatin remodeling through histone acetyltransferase activity and interaction with other transcriptional regulators. In this study, various hematological malignancies, including nine cell lines and 45 clinical samples (32 acute myeloid leukemias (AML), nine acute lymphoblastic leukemias (ALL), two cases of myelodysplastic syndrome (MDS), one multiple myeloma, and one chronic myelogenous leukemia in blast crisis), were examined to ask whether mutation of the CBP and p300 genes could be involved in leukemogenesis. The answer was approached by employing the reverse transcription-polymerase chain reaction and single-strand conformation polymorphism (RT-PCR/SSCP) technique and subsequent sequence analysis. A T-lymphoblastic cell line, CEM had an in-frame 21-base-pair deletion within the bromodomain of its p300 cDNA. Genomic DNA analysis revealed aberrant splicing caused by mutation of the acceptor site of intron 17 from ag to gg, which should interfere with catalytic step II of the pre-mRNA splicing reaction. In 1 MDS patient, a missense mutation was detected, which caused a replacement from Ser to Gly at codon 507 of p300. This is the first report of CBP/p300 mutations in leukemias, which might be relatively rare but nonetheless contribute to pathogenesis in some fraction of cases.

http://www.hubmed.org/display.cgi?issn=03043835&uids=15312679

Cytogenetic and hematological spontaneous remission in a case of acute myelogenous leukemia

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Cytogenetic and hematological spontaneous remission in a case of acute myelogenous leukemia.
Eur J Haematol. 2004 Sep ; 73(3): 219-22
Several cases of spontaneous remission (SR) interrupting the invariably progressive course of untreated acute myeloblastic leukemia (AML) have been reported so far. We shall add to this series the hematological and cytogenetic SR occurring in a 72-yr-old man affected by AML following myelodysplastic syndrome. At diagnosis cytogenetic analysis showed the 48, xy, del (6) (p22-pter), +13, +14 karyotype. Owing to a lobar pneumonia, the chemotherapy was deferred and a broad spectrum antibiotic therapy was established. Supportive care included red cells and platelet transfusions and low-dose corticosteroid. Two months later, after the pneumonia had completely disappeared, a complete remission, lasting about 5 months, was documented on bone marrow morphological and cytogenetical examination, although some degree of myeloid dysplasia persisted. Possible mechanisms of the various SRs described during the course of AML are discussed with a review of the literature.

http://www.hubmed.org/display.cgi?issn=09024441&uids=15287921

Initial expression of interferon alpha receptor 2 (IFNAR2)

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Initial expression of interferon alpha receptor 2 (IFNAR2) on CD34-positive cells and its down-regulation correlate with clinical response to interferon therapy in chronic myelogenous leukemia.
Eur J Haematol. 2004 Sep ; 73(3): 191-205
In order to investigate the mechanism of interferon-alpha (IFNalpha) action in the treatment of chronic myelogenous leukemia (CML), we examined surface expressions of both type I interferon receptor 1 (IFNAR1) and 2 (IFNAR2) subunits on CD34-positive cells in bone marrow (BM) in a total of 57 CML patients. Initial cell-surface IFNAR2 expression at diagnosis assessed by flow cytometry widely distributed but showed overall significantly higher expression in CML patients when compared with normal controls. In 15 fresh patients who subsequently received IFNalpha therapy, IFNAR2 expression at diagnosis was significantly higher in cytogenetic good responders than in poor responders. Down-regulation of IFNAR2 expression during IFNalpha therapy was observed only in good responders but not in poor responders. In addition to protein level, both initial high IFNAR2c mRNA expression level and its down-regulation during IFNalpha therapy, in purified CD34-positive cells, were also observed only in good responders. In contrast to IFNAR2, cell-surface IFNAR1 expression was generally lower than IFNAR2, and correlation between either the pretreatment level or down-regulation of IFNAR1 and clinical response was not evident. With in vitro IFNalpha stimulation, CD34-positive cells showed down-regulations of cell-surface IFNAR2, and IFNAR1 to a lesser extent, in one good-responder patient, but not in one poor-responder patient. Serum soluble interferon receptor (sIFNR) was higher in untreated CML patients than in normal controls, without any correlation with clinical response to IFNalpha. Thus, the pretreatment protein and mRNA expression levels of IFNAR2 and their down-regulations during IFNalpha therapy correlate well with IFNalpha response in CML patients.

http://www.hubmed.org/display.cgi?issn=09024441&uids=15287917

Name Chosen For New Unified CML Site

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 CMLHope.Com 

The name CMLHOPE.COM has been chosen for the new unified CML site that will soon be lauched. The new site will serve as a central portal for the various services and resources that are provided worldwide for CML patients through the network of the CML Support Group. The name reflects the many advances in treatment methods that have been made since the CML Support Group was started in 1997 and the promising research and new treatment methods that are anticipated in the future.

CMLHOPE.COM will be the home of both existing and new resources for Chronic Myelogenous Leukemia (aka Chronic Myeloid Leukemia) (CML) patients, caregivers, and professionals.  

CML Support Group
The largest support group in the world for CML patients. Founded in 1997.

CML Support News
Daily newsfeed of the latest medical articles and news on CML.

CML Meetup
An international network of local support groups for CML patients which covers over 60 countries. New features of Meetup will allow those interested to apply to become local CML organizers in their own community to schedule local support group and social events.

[new] CML Forum
The new site will feature a new state of the art web message board system which can be used by registered members of CMLHOPE.COM

[new] CML Links
Links to selected and trusted sources of information for CML patients, caregivers, and professionals

[new] CML Clinical Trials
An easy to use search function will locate the most current CML Clinical Trials.

[new] CML Chat
In addition to Zavie’s regular chats on Yahoo, new chat technology is also being considered for inclusion in the new site to allow more to participate in regular chats.

[new] CML Store
The new CML Store will provide a selection of CMLHOPE.COM and CML Meetup merchandise including shirts, cups, and other logo merchandise which will be available for purchase. There will also be a book section that will allow CML patients to purchase books that other CML patients have found useful.

[new] CML ADVOCACY
The new site will include an automated section for letter writing that will allow CML patients, caregivers, and others to write letters to their local newspapers and to state and federal elected officials on issues that are of concern to the CML community. Messages will be sent electronically and will be at no cost to users.

[new] CML Archives
The new site will include backup archives of new messages starting in 2004 with improved search access.

Additional features and resources will be announced after the site has launched.

c 2004 CMLHOPE.COM

 

Pic Of The Day

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An athlete in a Single Sculls practices at the Schinias Rowing and Canoeing Center, outside Athens.

Pic Of The Day

Posted by rob on August 18, 2004 under Uncategorized | Be the First to Comment

British riders cycle in line during a training session at the Velodrome in Athens three days before the start of the cycling track competition at the 2004 Olympic Games

New Gleevec Plant To Be Located In Singapore

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AUG 18, 2004
Biomed boost from Swiss giant

Novartis’s $310m investment in a drug plant will help Singapore’s push to be a centre for high-value pharmaceuticals

By Narendra Aggarwal

IN A major boost to Singapore’s fledgling biomedical sector, Swiss pharmaceutical giant Novartis is making its biggest investment in Asia, by building a drug plant here at a cost of US$180 million (S$310 million).

Novartis, the world’s fifth-largest seller of prescription drugs, with sales of US$25 billion last year, said yesterday that when fully operational by 2008, its new Singapore facility would create more than 150 jobs.

The announcement is the latest boost to Singapore’s ambitions to become a strategic centre for the production of high-value pharmaceuticals.

The Republic is promoting the fast-growing biomedical sector as a key pillar of the country’s all-important manufacturing sector and has set a goal of achieving output of $24 billion over the next decade, as well as providing 15,000 jobs.

And the industry is well on track, with output expected to hit $12 billion this year, a year ahead of schedule.

Novartis Pharma AG’s new pharmaceutical production facility will be built in the Tuas biomedical park and will focus on the bulk production of Novartis products, such as anti-hypertension drug Diovan and abdominal discomfort treatment drug Zelnorm.

It will also produce Gleevec, a new cancer drug, which is one of the company’s leading revenue drivers.

‘The new Singapore facility will enhance and complement our existing network of pharmaceutical production plants by producing tablets for the global market,’ said the head of Novartis Pharma Technical Operations, Dr Andreas Rummelt.

‘We have been under-represented in Asia… As we needed more capacity to meet growing global demand we looked at several locations like Singapore, India and China,’ he said in a phone interview from his Basel office.

‘Singapore is an ideal location for us,’ he said, citing the Government’s strong support for the sector, intellectual property protection, political and economic stability, and the availability of scientific expertise as some of the Republic’s attractions.

Dr Rummelt said that construction of the plant is expected to begin towards the end of the year, with operations beginning in 2007.

Yesterday’s announcement follows the opening last month of the US$122 million non-profit Novartis Institute for Tropical Diseases in collaboration with the Economic Development Board. And Novartis’ CIBA Vision business unit is in the process of building a contact lens manufacturing facility here.

Two key Novartis’ rivals also announced moves here recently.

Last month, United States-based Pfizer, the world’s biggest pharmaceutical company, unveiled a new $600 million plant just after closest rival, Britain’s GlaxoSmithKline opened another facility, taking its total investment here past S$1 billion.

http://straitstimes.asia1.com.sg/storyprintfriendly/0,1887,267639,00.html?

Beta-D-glucan as a diagnostic adjunct for invasive fungal infections:

Posted by rob on August 17, 2004 under Uncategorized | Be the First to Comment

Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.
Clin Infect Dis. 2004 Jul 15; 39(2): 199-205
The Glucatell (1–>3)- beta-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of >or=60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and >or=96% for >or=2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.

http://www.hubmed.org/display.cgi?issn=15376591&uids=15307029

Pic Of The Day

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A twisted sign marking U.S. Route 17 stands in front of destroyed mobile homes near Arcadia, Florida

HealthWatch: CML

Posted by rob on August 16, 2004 under Uncategorized | Be the First to Comment

August 16, 2004 –

Ben Swann-KFOX Morning News Anchor/Reporter

It’s been 5-years since the cancer drug Gleevec was introduced in clinical trials to treat a Chronic Leukemia. Gleevec was so successful, that it received one of the fastest approvals ever for a cancer therapy. Now researchers are studying it’s application in other cancers.

You’d never know looking at him now that 4-years ago, Ken Geihsler was fighting for his life. He was diagnosed with chronic myelogenous leukemia, or CML. After six months on interferon, his disease was progressing and he was suffering side effects. All that changed when he entered a clinical trial at M. D. Anderson Cancer Center studying Gleevec.

Ken Geihsler-Patient: “I’ve been on the study four years. The results have been fantastic, as far as I’m concerned. I don’t even feel like I’m sick. In fact, people keep saying that there’s no way that you can absolutely have cancer or have leukemia the way you look, the way you act, the energy you have and all the activities you are involved in.”

Gleevec is what is known as a targeted therapy; in this case, a drug specifically designed to inhibit certain proteins involved in the development of CML.

Dr. Hagop Kantarjian-M. D. Anderson Cancer Center: “It’s like a magic bullet that removes the protein that causes the cancer cells to become cancer and to progress, and so by removing the feeding system or the protein, those cancer cells die, and the normal cells come back. So, in the past, we talked about an average survival in CML of 3 to 5 years. Now, we estimate that the average survival is going to be 15 years and that perhaps half of the patients will have complete elimination of the disease.”

The success of Gleevec in treating CML, demonstrated to researchers how effective targeted therapies can be in cancer treatment. The concept of targeted therapy is being studied in a wide range of cancers. Meanwhile, Ken whose 66-years-old, continues on Gleevec, with minimal side effects.

Ken Geihsler-Patient: “I certainly will not object to taking the Gleevec for the rest of my life.”

If you would like more medical news, visit our health partners websites:

M.D. Anderson Cancer Center:http://www.mdanderson.org/

The Mayo Clinic:http://www.medicaledge.org

Baylor College of Medicine:http://public.bcm.tmc.edu/