Researchers Uncover Clues That May Lead To Better Therapies For Children With T-Cell Acute Lymphocytic Leukemia

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Pediatrics / Children's Health
Article Date: 16 Sep 2006 - 0:00 PST

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Researchers' discovery of clues to the cause of T-cell acute lymphoblastic leukemia (T-ALL) - a form of pediatric cancer that has a very poor prognosis - could lead to the development of new targeted therapies for this extremely difficult disease.

The researchers, led by Michelle Kelliher, PhD, of the University of Massachusetts Medical School, will report on their findings in the November issue of the journal Molecular and Cellular Biology.

The researchers report that abnormal expression of one gene - Notch 1 - activates another gene - c-myc - which is a known cause of leukemia and lymphoma. Recent studies have shown that a majority of T-ALL cases carry mutations that abnormally activate the Notch 1 gene.

Dr. Kelliher and her colleague, Anthony Capobianco, PhD., engineered mice in which abnormal Notch expression can be turned on and off and found that when Notch 1 was active, mice developed aggressive T-cell cancers as soon as seven weeks after birth. These tumors regressed when Notch 1 was turned off, showing that Notch 1 not only can cause these cancers but is needed for their continued growth.

Jennifer Calvo a graduate student in the Kelliher lab (now a postdoctoral fellow at Novartis) then made T-ALL cell lines from the mouse tumors and watched as the leukemic cells died when Notch1 was turned off. Using this system, Calvo identified the oncogene and key cell cycle regulator, c-myc, as a critical player in how Notch 1 stimulates leukemic growth.

These new findings suggest that therapies that target c-myc directly might also benefit T-ALL patients.

"Outcomes for children with acute lymphocytic leukemia have improved dramatically in the past few decades - to approximately 75 percent - but that 25 percent, many of whom have T-ALL, are not being cured," said Dr. Kelliher. "We are hopeful that these findings will lead to more successful treatment of these children."

Drs. Kelliher and Capobianco are recipients of Scholar awards from The Leukemia & Lymphoma Society - a program that provides funding to highly qualified investigators who have demonstrated over a period of not less than five years his or her ability to conduct original research on leukemia, lymphoma or myeloma.

"The goal of the Scholar program is to help advance promising original research with the potential to have the highest impact on blood cancers," said Deborah Banker, the Society's Vice President for Research Communications. "This research shows great promise in leading to more effective treatments for T-ALL patients."

Dr. Kelliher said that the Society's support was fundamental in moving her research forward.

"I am truly grateful to The Leukemia & Lymphoma Society for having confidence in our work and providing our group with this funding," she said. "I am optimistic that our efforts will improve the outcomes for leukemia patients."

About The Leukemia & Lymphoma Society

The Leukemia & Lymphoma Society(R), headquartered in White Plains, NY, with 66 chapters in the United States and Canada, is the world's largest voluntary health organization dedicated to funding blood cancer research and providing education and patient services. The Society's mission: Cure leukemia, lymphoma, Hodgkin's disease and myeloma, and improve the quality of life of patients and their families. Since its founding in 1949, the Society has invested more than $483 million in research specifically targeting leukemia, lymphoma and myeloma. Last year alone, the Society made 4.2 million contacts with patients, caregivers and healthcare professionals.

The Leukemia & Lymphoma Society
http://www.LLS.org