Improving Diagnostic Methods for Minimal Residual Disease Detection (MRD) in Childhood Acute Lymphoblastic Leukemia (ALL)

Introduction: Our group has shown the high frequency and the prognostic value of IKZF1 deletions and TP53 alterations in relapsed childhood ALL. Interestingly, IKZF1 deletions and TP53 alterations predicted subsequent relapses among patients with MRD good response. We wanted to test the hypothesis whether the use of these two functional markers for MRD quantification provide additional information about the kinetics of the subsequent relapse driving clone.

Methods: For MRD quantification, IKZF1 and TP53 specific real-time quantitative (RQ) PCR targeting intragenic consensus breakpoints are used and point mutation specific RQ-PCR will be established. MRD values are compared to data obtained with conventional T-cell receptor and immunoglobulin gene rearrangements (TCR/IG markers).

Results: First results demonstrate that the IKZF1 deletions serve as reliable and sensitive MRD markers and provide quantitative results which are concordant with those obtained by conventional TCR/IG markers.

Conclusion: Thus, the IKFZ1 deletions could enrich the repertoire of markers for MRD response measurement, which is of particular importance for patients with insufficient or lacking TCR/IG markers.