Leukemia Model Created Using Human Cells

Memorial Sloan-Kettering Cancer Center
Tuesday, 1 January 2002

For the first time, scientists have been able to use normal, human stem cells to model a common type of leukemia in the laboratory. A genetic mutation linked to leukemia was combined with human stem cells to create a model of acute myelogenous leukemia (AML). Thus researchers have been able to produce in a Petri dish results similar to what occurs when a healthy person develops this type of leukemia. This work by researchers at Memorial Sloan-Kettering Cancer Center, published in the January 2002 issue of Blood, has been designated a "Plenary Paper" by the peer reviewed journal due to its significance.

While it is common to use mouse models to study human diseases, the available modelling in mice or human cell lines have not proven satisfactory for many types of AML. "We wanted to move beyond the currently available models to study adult AML," said Dr. Stephen D. Nimer, head of the Division of Hematologic Oncology at Memorial Sloan-Kettering and senior author of the study. "The model of human leukemia that we have established should provide a more accurate understanding of the genetic basis of human leukemia which could enable us to attack leukemia more effectively."

Acute Myeloid Leukemia is the most common type of acute leukemia, accounting for almost one third of the estimated 28,800 new cases diagnosed in 2001 as well as one third of the estimated deaths. While the causes of most leukemia are not known, leukemic cells often contain a specific and recurring chromosomal abnormality. In AML, the AML1-ETO fusion protein is the most common genetic mutation linked to development of the disease.

For this study, AML1-ETO was put into normal human hematopoietic stem cells and progenitor cells at the earliest possible stage. Expression of the AML1-ETO fusion protein inhibited the growth of non-stem cells but enhanced the growth and self-renewal of real stem cells that were nearly immortal.

"Using human stem cells and an efficient gene delivery system, we were able to target the exact cell affected in human leukemia and generate a more realistic model for studying AML," explained James C. Mulloy, Ph.D., a senior research scientist at Sloan-Kettering Institute and first author of the study. "This will allow us to define the abnormalities that constitute human leukemia more rapidly and learn how to disrupt or reverse them."

The study was the result of a collaboration of the Laboratory of Molecular Hematopoiesis and the Laboratory Developmental Hematopoiesis at Sloan-Kettering Institute and the Division of Hematologic Oncology at Memorial Sloan-Kettering Cancer Center.

Additional study co-authors are Jorg Cammenga, Karen L. MacKenzie, Francisco J. Berguido and Malcolm A.S. Moore.

The National Institutes of Health, Panayiota Makkos Memorial Fund, and the Gar Reichman Fund of the Cancer Research Institute funded this work.

Memorial Sloan-Kettering Cancer Center is the world's oldest and largest institution devoted to prevention, patient care, research and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide.

Note: This study entitled, "The AML1-ETO fusion protein promotes the expansion of human hematopoietic stem cells", is available on line at www.bloodjournal.org.

For more information, or to contact Memorial Sloan-Kettering Cancer Center, see their website at: www.mskcc.org