IKZF1plus Defines a New Minimal Residual Disease-Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.

IKZF1plus Defines a New Minimal Residual Disease-Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.
This paper from the International BFM Study Group further defines the IKZF1 gene as a very poor prognostic marker in pediatric B-cell precursor ALL. The study group looked to refine the prognostic strength of the IKZF1 deletion by looking at the effect of the co-occurring gene deletions.
The study analysed 991 patients with B-cell precursor ALL from the European group (AIEOP-BFM) trial with complete information for copy number alterations of major genes associated with outcome in ALL. There was also a smaller replication cohort of 417 patients from the same trial.
The study then analysed gene combinations and evaluated patient outcomes including how gene combinations affected outcomes combined with MRD status.
"IKZF1plus" was defined as an IKZF1 deletion co-occurring with deletions in CDKN2A, CDKN2B, PAX5 or PAR1 in the absence of a deletion in the ERG gene.
The IKZF1plus group made up of 6% of patients in the cohort of children with B-cell precursor ALL (n=63). The 5-year EFS for this IKZF1plus group was 53% compared to 79% for those with lone IKZF1 deletions and 87% for patients who lacked the IKZF1 deletion altogether. The 5-year EFS when combining the IKZF1plus combination with MRD was 95% for standard risk MRD versus 40% for intermediate MRD and 30% for high-risk MRD.
Given differences in therapy and timing/method of MRD measurement it's not clear whether these results can be generalized to other study groups.
The use of the IKZF1 deletion in combination with specific additional single gene deletions – the so-called IKZF1plus – provides an independent and strong molecular stratification marker in addition to MRD measurements. The IKZF1plus group with positive MRD are a particularly high-risk group and should be assigned additional/experimental treatments, which will be evaluated in the upcoming AIEOP-BFM ALL 2017 trial. On the other hand, the IKZF1plus genotype loses prognostic significance when MRD is negative.