The risk of relapse and death in children with acute myeloid leukemia (AML) after induction therapy could be predicted by high expression of Wilms tumor gene 1 (WT1)

08-25-2006

According to a recently published article from France, "To determine whether minimal residual disease (MRD) measured by WT1 expression is a prognostic marker in pediatric AML, we quantified WT1 transcript by real-time quantitative-polymerase chain reaction in 92 AML at diagnosis and during follow-up. Patients (median age, 6 years; cytogenetics, favorable 27%, intermediate 59%, poor 13%) were treated between 1995 and 2002 and enrolled in Leucemii Myeloblastique Enfant (LAME) 89/91, LAME 99 pilot study and Acute Promyelocytic Leukemia French collaborative protocols. With a median follow-up of 26 months, event-free survival was 56% with a standard deviation (SD) of 5% and overall survival of 62.5% with an SD of 6%."

"WT1 copy number was normalized by TATA box binding protein gene transcripts and expressed as WT1/TBP X 1,000 ratio," explained H. Lapillonne and colleagues, Hopital Armand Trousseau. "Median WT1 ratio in normal patient controls was 12 (range, 0 to 57). A level over 2 SD than normal bone marrow controls (i.e., WT1 ratio >50), was considered as significant overexpression. At diagnosis, WT1 overexpression was detected in 78% of patients (72 of 92 patients; median copy ratio, 2231). The WT1 values were significantly higher (p=.01) in favorable cytogenetics and lower (p<.0001) in M5-FAB subtype, 11q23 rearrangements (p<.001), and infants (p=.003) and demonstrate a strong correlation with fusion transcript AML1-ETO, PML-RAR alpha expression.

"After induction treatment, WT1 ratio was analyzed in 46 of 72 patients and found above 50 in 9 of 36 patients and 5 of 25 patients at D35-50 and 3 to 5 months, respectively. WT1 ratio >50 after induction is an independent prognostic risk factor of relapse (p=.002) and death (p=.02)."

The researchers concluded, "WT1 quantification is an informative molecular marker for MRD in pediatric AML and is now performed as prospective analysis in ELAM02 protocol."

Lapillonne and colleagues published their study in the Journal of Clinical Oncology (High WT1 expression after induction therapy predicts high risk of relapse and death in pediatric acute myeloid leukemia. J Clin Oncol, 2006;24(10):1507-1515).

For more information, contact H. Lapillonne, Hopital Armand Trousseau, Service Hematology & Oncology Pediatrics, Hematology Laboratory, 26 Avenue Arnold Netter, F-75012 Paris, France.

Keywords: Paris, France, Acute Myeloid Leukemia, Bone Marrow, Diagnosis, Diagnostics, Genetics, Oncology, Prognosis, Prognostics, Induction Therapy, High Expression, Wilms Tumor Gene 1.

This article was prepared by Cancer Vaccine Week editors from staff and other reports. Copyright 2006, Cancer Vaccine Week via NewsRx.com.