Les marqueurs IKZF1 et IG combinés : nouveaux outils pour le diagnostic et le suivi des LAL-B tunisiennes

Abstract

Introduction The monitoring of minimal residual disease (MRD) approach in patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) allows an early detection of residual clones inducing relapses and therefore appropriate therapy strategy. The molecular markers may identify and quantify the residual blasts in B-ALL with normal cytology. In this study, we aimed to use combined IKZF1, IGH and IGK immunoglobulin genes for diagnosis and MRD monitoring in B-ALL sample using MLPA, multiplex PCR and real-time quantitative PCR. Material We showed that multiplex PCR and MLPA are necessary and complementary to detect IKZF1 deletions. Results We have identified at the diagnosis clonal IGH rearrangement (VH3–JH5) and IKZF1 deletion (Δ4–7), which we have used it for MRD evaluation after induction chemotherapy. Despite the absence of chromosome abnormality, the patient may be classified in high-risk group with a relapse rate of residual blasts > 10−4 and sensitivity up to 10−5. This molecular approach enabled the patient's stratification, which was overlooked by classical methods. Conclusion The combined IKZF1 and immunoglobulin genes will be used as appropriate molecular tools for diagnosis and MRD assessment of B-lineage leukemias and introduced as a routine tests in Tunisian clinical laboratories. They will be useful to stratify patients into risk groups leading to better treatment strategy.