N-Myc

"By eliminating IL-3 from the culture, we were able to unmask the apoptotic effect of N-Myc, which greatly increased cell death," Grosveld said.

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Mice that received bone marrow cells genetically engineered to overexpress N-Myc developed AML and died within 50 days.

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Grosveld's team believes that the AML does not result from N-Myc overexpression alone.

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"So those findings in our lab suggest once again that N-Myc is linked to AML."

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The researchers showed that when myeloid cells overexpressing N-Myc were placed in culture dishes that lacked an anti-apotosis, growth-promoting protein called IL-3, about 75 percent of the cells died within 24 hours.

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Previously, researchers had reported that overexpression of N-Myc as a result of amplification of the N-Myc gene occurs in a variety of cancers such as neuroblastoma, a common solid tumor of childhood that arises from nervous system cells; retinoblastoma, a cancer of the eye; and Wilms tumor, a cancer of the kidney.

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"We speculated that genes that are expressed in a MYCN-dependent manner might be required specifically for the growth of MYCN-amplified neuroblastomas and that MYCN-amplified neuroblastomas might depend not only on N-Myc itself, but also on upstream regulatory factors or downstream target genes," explains senior study author, Dr Martin Eilers, from the University of Wurzburg.

The Earth Times Online Newspaper 2009

"Our results show that stabilization of N-Myc is a critical oncogenic function of Aurora A in childhood neuroblastoma; the challenge will now be to find ways to interfere with this function in order to find new approaches for the therapy of these tumours," says Dr. Eilers.

The Earth Times Online Newspaper 2009

Artificially forcing overexpression of N-Myc in bone marrow cells of mice strongly promotes this type of leukemia; that finding is significant since N-Myc overexpression frequently occurs in human AML.

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The team also showed that myeloid cells that were genetically engineered to overexpress N-Myc became immortalized, or had an unlimited life span.

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