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COG P9407 trial: MLL partner genes identified, linked to outcomes
51st ASH Annual Meeting
Results of the Children’s Oncology Group P9407 pilot trial identified specific MLL partner genes and define their associations with outcome in infants with acute lymphoblastic leukemia.
“The ability to characterize acute lymphoblastic leukemia based on specific partner genes may provide a new way to determine whether infants with ALL in which the partner genes of MLL are different will benefit from specific types of treatment,” Carolyn A. Felix, MD,professor of pediatrics at the Children’s Hospital of Philadelphia, Penn., said in a press release. “We hope that these findings will help lead to the development of new, molecularly targeted therapies for infants with leukemia.”
Researchers from the Children’s Hospital of Philadelphia, in collaboration with the Children’s Oncology Group, determined the specific partner genes involved in MLL translocations in infants with ALL enrolled in the COG P9407 trial.
Researchers enrolled 221 infants with ALL and utilized methods, including Southern blot analysis and reverse transcriptase polymerase chain reaction, to identify MLL translocations and specific partner genes at the levels of the genes and chromosomes. They then determined how MLL translocations with different partner genes affected prognosis and examined their relationship to classical prognostic factors.
Seventy-four percent of infant leukemia cells had an MLL translocation. The most common partner genes of MLL were AF4, ENL and AF9. Worse patient survival was associated with the two most common partner genes of MLL: AF4, which is located on chromosome 4 and ENL, which is located on chromosome 19.
When the MLL gene fused with AF9, which is located on chromosome 9, better patient outcomes were observed. Worse outcome was noted when AF4 or ENL occurred as partner genes in infants who were aged less than 90 days at diagnosis. Translocations fusing MLL with AF4 were linked to an elevated white blood cell count, while those fusing MLL with AF9 were linked to a lower white blood cell count.
“Infant ALL is a very heterogeneous disease with respect to outcome and that outcome is dictated by a complex interplay of the host factor of age at diagnosis, the underlying types of MLL translocations with different partner genes driving the biology, the white blood cell count and the treatment protocol,” Felix told HemOnc Today.
“There is tremendous urgency for better more effective treatments for infant ALL where survival is so far behind what has been achieved in children; better understanding the disease biology in the context of this complex interplay is extremely critical to finding better treatments,” she said. - by Christen Haigh
For more information:
- Robinson BW. #907. Presented at: 51st ASH Annual Meeting and Exposition, Dec. 4-8, 2009, New Orleans.
