Newly Found Leukemia Genes

[Guest guest]

" For instance, we found that one of the genes, called Spic, was disrupted in

nine distinct myeloid leukaemia tumours in our mice. An event of this frequency

merits study in human cancer and, when we take into account recent studies that

have found this gene has a role in the development of white blood cells, we can

be even more optimistic about the potential of this finding. "

" Other genes identified include Hdac7, which is known to participate in the

creation of white blood cells in the thymus but has, to date, not been studied

in the context of blood cancers; and Bcl9, a gene whose human equivalent is

thought to be involved in leukaemia. Now teams can begin to understand - at a

biological level - which, among the thousands of mutations present, is the

cause. "

Publication Details:

Rad R et al. (2010) PiggyBac Transposon Mutagenesis: A Tool for Cancer Gene

Discovery in Mice. Science.

Funding:

This work was supported by the Wellcome Trust and the German Research

Foundation. Source: Don , Wellcome Trust Sanger Institute

http://www.medicalnewstoday.com/articles/204754.php

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" Cepheid announced an exclusive collaboration with Novartis for the

commercialization of a test for monitoring the BCR-ABL gene transcript in

peripheral blood specimens from patients diagnosed with Philadelphia

chromosome-positive chronic myelogenous leukemia (Ph+ CML). Together with other

lab tests, monitoring levels of BCR-ABL transcripts in Ph+ CML patients will aid

in patient management.

" The collaboration reflects the commitment shared by Novartis and Cepheid to

deliver the benefits of an FDA-cleared/approved molecular test that reports

results which are linked to an internationally accepted standard called the

" International Scale " (IS). With the development of the class of drugs called

tyrosine kinase inhibitors, Ph+ CML patients have access to the broadest range

of therapeutic options ever available. A standardized molecular monitoring

BCR-ABL test with greater reproducibility is expected to support optimal patient

management decisions. By moving to a rigorously developed,

regulatory-cleared/approved test which is also linked to the IS, the

collaboration aims to reduce the variability that is currently inherent in

BCR-ABL testing. "

http://www.medicalnewstoday.com/articles/203932.php

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" Swiss drug major Novartis (NOVN.VX) has entered an agreement with Synthetic

Genomics Vaccines Inc (SGVI) to apply " synthetic genomics " technologies to

accelerate the production of the influenza seed strains required for vaccine

manufacturing and so significantly reduce the time to ramp up production of a

new flu vaccine. "

http://tinyurl.com/23lvzc2

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" Last week pharmaceutical executives met as a result of a drugs recall after a

pill mix up of breast cancer pills. The drug, Fresenius Kabi’s anastrozole (a

generic copy of AstraZeneca’ Arimidex), was made by the German company’s

subsidiary in India. The ingredient mix up led to the voluntary recall of 7,192

bottles, each containing 30 tablets. "

http://tinyurl.com/24monex

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" A novel technology can make nanoscale protein measurements, which scientists

can use in clinical trials to learn how drugs work. Using new technologies

makes it possible to measure effects of therapeutic agents in tumor cells and

different cell populations within our patients. Now that we can make these

measurements, we are one step closer to being able to tailor therapy for each

patient. "

http://www.medicalnewstoday.com/articles/202814.php

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Drug Sales In The Leukemia Market Will Be Driven By Therapies From Novartis,

Bristol-Myers Squibb, Biogen Idec, Roche And Cephalon.

'Decision Resources, one of the world's leading research and advisory firms for

pharmaceutical and healthcare issues, finds that growth in the leukemia market

will be driven mostly by chronic myelogenous leukemia (CML) therapies

(Novartis's Gleevec and Tasigna and Bristol-Myers Squibb's Sprycel) and chronic

lymphocytic leukemia (CLL) therapies (Biogen Idec/Roche's Rituxan and Cephalon's

Treanda) until 2015, when patent and orphan-drug exclusivities of key brands

will impact the sustainability of this growth. "

Decision Resources, one of the world's leading research and advisory firms for

pharmaceutical and healthcare issues, finds that growth in the leukemia market

will be driven mostly by chronic myelogenous leukemia (CML) therapies

(Novartis's Gleevec and Tasigna and Bristol-Myers Squibb's Sprycel) and chronic

lymphocytic leukemia (CLL) therapies (Biogen Idec/Roche's Rituxan and Cephalon's

Treanda) until 2015, when patent and orphan-drug exclusivities of key brands

will impact the sustainability of this growth.

Decision Resources, one of the world's leading research and advisory firms for

pharmaceutical and healthcare issues, finds that growth in the leukemia market

will be driven mostly by chronic myelogenous leukemia (CML) therapies

(Novartis's Gleevec and Tasigna and Bristol-Myers Squibb's Sprycel) and chronic

lymphocytic leukemia (CLL) therapies (Biogen Idec/Roche's Rituxan and Cephalon's

Treanda) until 2015, when patent and orphan-drug exclusivities of key brands

will impact the sustainability of this growth.

http://www.medicalnewstoday.com/articles/202351.php

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" Researchers at UCLA's Jonsson Comprehensive Cancer Center have discovered a new

cell signaling pathway that controls cell growth and development, a pathway

that, when defective, helps promote the formation of several major forms of

human cancer, including lymphoma and leukemia. The new pathway, part of a global

DNA damage response, turns off 136 genes, including some that have are known to

cause cancer because, unchecked, they can promote aberrant cell division.

" It's important to make sure this pathway works correctly, because it prevents

cells from dividing excessively " said Dr. Teitell, a professor of

pathology and laboratory medicine, a Jonsson Cancer Center researcher and senior

author of the study. " When this pathway is defective, cancers can happen. "

http://www.medicalnewstoday.com/articles/202298.php

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The recent development of hyperpolarized 13C magnetic resonance spectroscopic

imaging provides a novel method for in vivo metabolic imaging with potential

applications for detection of cancer and response to treatment.

Chemotherapy-induced apoptosis was shown to decrease the flux of hyperpolarized

13C label from pyruvate to lactate due to depletion of NADH, the coenzyme of

lactate dehydrogenase. In contrast, we show here that in PC-3MM2 tumors,

inhibition of platelet-derived growth factor receptor with imatinib reduces the

conversion of hyperpolarized pyruvate to lactate by lowering the expression of

lactate dehydrogenase itself. This was accompanied by reduced expression of

vascular endothelial growth factor and glutaminase, and is likely mediated by

reduced expression of their transcriptional factors hypoxia-inducible factor-1

and c-Myc. Our results indicate that hyperpolarized 13C MRSI could potentially

detect the molecular effect of various cell signaling inhibitors, thus providing

a radiation-free method to predict tumor response. Cancer Res; 70(19); 7400–10.

©2010 AACR.

http://tinyurl.com/286plrx

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DLI Infusions

" Curative effects of graft-versus-leukemia–based therapies such as donor

lymphocyte infusion (DLI) for chronic myelogenous leukemia (CML) may result from

immunologic ablation of self-renewing CML progenitor cells. Patients who

achieved durable remissions after DLI developed a significant B-cell

lymphocytosis after treatment, which did not occur in patients who were

unresponsive to DLI. In this study, we identified antigen targets of this B-cell

response by probing two immunoproteomic platforms with plasma immunoglobulins

from seven CML patients with clinically apparent graft-versus-leukemia responses

after DLI. In total, 62 antigens elicited greater reactivity from post-DLI

versus pre-DLI plasma. Microarray analysis revealed that >70% of the antigens

were expressed in CML CD34+ cells, suggesting that expression in malignant

progenitor cells is a feature common to antibody targets of DLI. We confirmed

elevated expression of three target antigens (RAB38, TBCE, and DUSP12) in CML

that together consistently elicited antibody responses in 18 of 21 of an

additional cohort of CML patients with therapeutic responses, but not in normal

donors and rarely in non-CML patients. In summary, immunologic targets of

curative DLI responses include multiple antigens on CML progenitor cells,

identifying them as potential immunogens for vaccination and/or monitoring of

immunotherapeutics designed to eliminate myeloid leukemia stem cells. Cancer

Res; 70(3); 906–15 + "

http://tinyurl.com/22sz2s9

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FYI,

Lottie Duthu