Gene discovery could improve treatment for acute myeloid leukemia

Public release date: 13-Aug-2012
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Contact: Kimberly Newman
sciencenews@einstein.yu.edu
718-430-3101
Albert Einstein College of Medicine

August 13, 2012 ? (BRONX, NY) ? Scientists at Albert Einstein College of Medicine of Yeshiva University have made a discovery involving mice and humans that could mean that people with acute myeloid leukemia (AML), a rare and usually fatal cancer, are a step closer to new treatment options. Their study results were published online today in Cancer Cell.

"We have discovered that a gene called HLX is expressed at abnormally high levels in leukemia stem cells in a mouse model of AML," said Ulrich Steidl, M.D., Ph.D., assistant professor of cell biology and of medicine at Einstein and senior author of the paper. (Gene expression is the process by which a gene synthesizes the molecule that it codes for; an "over-expressed" gene makes its product in abnormally high amounts.)

According to the National Cancer Institute, AML will be diagnosed in one of every 254 people during their lifetime. Most die within a few years of diagnosis. For the last several decades there has been little improvement in the survival rate for AML patients.

Dr. Steidl and his colleagues found that over-expression of the HLX gene in mice caused blood-forming stem cells to become dysfunctional and develop into abnormal progenitors (biological ancestors) of white blood cells that failed to differentiate into normal blood cells. Instead, those early, abnormal white cells formed duplicates of themselves.

The researchers then analyzed HLX expression data collected from 354 AML patients and found that 87 percent of them were over-expressing HLX compared with HLX expression in healthy individuals. And among patients expressing HLX at high levels in an even larger cohort of 601 patients: the greater their degree of HLX expression, the worse their survival chances.

Importantly, when Dr. Steidl's team used a laboratory technique to "knock down" HLX expression in AML cells taken from a mouse model of AML and from AML patients, proliferation of leukemia cells was greatly suppressed in both cases. And when the researchers knocked down HLX expression in mouse AML cells and human AML cells and then transplanted both types of cancer cells into healthy mice, those mice lived significantly longer compared with mice that received unaltered AML cells.

These findings suggest that targeting elevated HLX expression may be a promising novel strategy for treating AML.

"HLX is clearly a key factor in causing the over-production of white cells that occurs in AML," said Dr. Steidl. "Our research is still in its early stages, but we're looking towards developing drugsso we can improve treatment for AML and possibly other types of cancer." Einstein has filed a patent application related to this research. The HLX technology is available for licensing.

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The group's paper is titled, "H2.0-like homeobox (HLX) regulates early hematopoiesis and promotes acute myeloid leukemia." In addition to Dr. Steidl, who is also the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein, other Einstein authors include Ashley Pandolfi, M.S., Boris Bartholdy, Ph.D., Laura Barreyro, M.S., Britta Will, Ph.D., Michael Roth, M.D., Ujunwa C. Okoye-Okafor, M.S., and Tihomira I. Todorova, B.Sc.. Additional contributors are Masahiro Kawahara, M.D., Ph.D. (Kyoto University, Kyoto, Japan); Maria Figueroa, M.D., and Ari Melnick, M.D. (Weill Cornell Medical College, New York, NY); and Constantine S. Mitsiades, M.D., Ph.D. (Dana Farber Cancer Institute and Harvard Medical School, Boston, MA).

The research was supported by grants from the Leukemia Research Foundation, NYSTEM, the National Cancer Institute (CA131503) of the National Institutes of Health, and the Gabrielle's Angel Foundation for Cancer Research.

About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. During the 2011-2012 academic year, Einstein is home to 724 M.D. students, 248 Ph.D. students, 117 students in the combined M.D./Ph.D. program, and 368 postdoctoral research fellows. The College of Medicine has 2,522 full time faculty members located on the main campus and at its clinical affiliates. In 2011, Einstein received nearly $170 million in awards from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center Einstein's founding hospital, and five other hospital systems in the Bronx, Manhattan, Long Island and Brooklyn, Einstein runs one of the largest post-graduate medical training programs in the United States, offering approximately 155 residency programs to more than 2,200 physicians in training. For more information, please visit www.einstein.yu.edu and follow us on Twitter @EinsteinMed.

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Public release date: 13-Aug-2012
[ | E-mail | Share ]

Contact: Kimberly Newman
sciencenews@einstein.yu.edu
718-430-3101
Albert Einstein College of Medicine

August 13, 2012 ? (BRONX, NY) ? Scientists at Albert Einstein College of Medicine of Yeshiva University have made a discovery involving mice and humans that could mean that people with acute myeloid leukemia (AML), a rare and usually fatal cancer, are a step closer to new treatment options. Their study results were published online today in Cancer Cell.

"We have discovered that a gene called HLX is expressed at abnormally high levels in leukemia stem cells in a mouse model of AML," said Ulrich Steidl, M.D., Ph.D., assistant professor of cell biology and of medicine at Einstein and senior author of the paper. (Gene expression is the process by which a gene synthesizes the molecule that it codes for; an "over-expressed" gene makes its product in abnormally high amounts.)

According to the National Cancer Institute, AML will be diagnosed in one of every 254 people during their lifetime. Most die within a few years of diagnosis. For the last several decades there has been little improvement in the survival rate for AML patients.

Dr. Steidl and his colleagues found that over-expression of the HLX gene in mice caused blood-forming stem cells to become dysfunctional and develop into abnormal progenitors (biological ancestors) of white blood cells that failed to differentiate into normal blood cells. Instead, those early, abnormal white cells formed duplicates of themselves.

The researchers then analyzed HLX expression data collected from 354 AML patients and found that 87 percent of them were over-expressing HLX compared with HLX expression in healthy individuals. And among patients expressing HLX at high levels in an even larger cohort of 601 patients: the greater their degree of HLX expression, the worse their survival chances.

Importantly, when Dr. Steidl's team used a laboratory technique to "knock down" HLX expression in AML cells taken from a mouse model of AML and from AML patients, proliferation of leukemia cells was greatly suppressed in both cases. And when the researchers knocked down HLX expression in mouse AML cells and human AML cells and then transplanted both types of cancer cells into healthy mice, those mice lived significantly longer compared with mice that received unaltered AML cells.

These findings suggest that targeting elevated HLX expression may be a promising novel strategy for treating AML.

"HLX is clearly a key factor in causing the over-production of white cells that occurs in AML," said Dr. Steidl. "Our research is still in its early stages, but we're looking towards developing drugsso we can improve treatment for AML and possibly other types of cancer." Einstein has filed a patent application related to this research. The HLX technology is available for licensing.

###

The group's paper is titled, "H2.0-like homeobox (HLX) regulates early hematopoiesis and promotes acute myeloid leukemia." In addition to Dr. Steidl, who is also the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein, other Einstein authors include Ashley Pandolfi, M.S., Boris Bartholdy, Ph.D., Laura Barreyro, M.S., Britta Will, Ph.D., Michael Roth, M.D., Ujunwa C. Okoye-Okafor, M.S., and Tihomira I. Todorova, B.Sc.. Additional contributors are Masahiro Kawahara, M.D., Ph.D. (Kyoto University, Kyoto, Japan); Maria Figueroa, M.D., and Ari Melnick, M.D. (Weill Cornell Medical College, New York, NY); and Constantine S. Mitsiades, M.D., Ph.D. (Dana Farber Cancer Institute and Harvard Medical School, Boston, MA).

The research was supported by grants from the Leukemia Research Foundation, NYSTEM, the National Cancer Institute (CA131503) of the National Institutes of Health, and the Gabrielle's Angel Foundation for Cancer Research.

About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. During the 2011-2012 academic year, Einstein is home to 724 M.D. students, 248 Ph.D. students, 117 students in the combined M.D./Ph.D. program, and 368 postdoctoral research fellows. The College of Medicine has 2,522 full time faculty members located on the main campus and at its clinical affiliates. In 2011, Einstein received nearly $170 million in awards from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center Einstein's founding hospital, and five other hospital systems in the Bronx, Manhattan, Long Island and Brooklyn, Einstein runs one of the largest post-graduate medical training programs in the United States, offering approximately 155 residency programs to more than 2,200 physicians in training. For more information, please visit www.einstein.yu.edu and follow us on Twitter @EinsteinMed.

---

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Source: http://www.eurekalert.org/pub_releases/2012-08/aeco-gdc081312.php

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