Minimal residual disease detection in Tunisian B-acute lymphoblastic leukemia based on immunoglobulin gene rearrangements

Abstract

IGH gene rearrangement and IGK-Kde gene deletion can be used as molecular markers for the assessment of B lineage acute lymphoblastic leukemia (B-ALL). Minimal residual disease detected based on those markers is currently the most reliable prognosis factor in B-ALL. The aim of this study was to use clonal IGH/IGK-Kde gene rearrangements to confirm B-ALL diagnosis and to evaluate the treatment outcome of Tunisian leukemic patients by monitoring the minimal residual disease (MRD) after induction chemotherapy. Seventeen consecutive newly diagnosed B-ALL patients were investigated by multiplex PCR assay and real time quantitative PCR according to BIOMED 2 conditions. The vast majority of clonal VH-JH rearrangements included VH3 gene. For IGK deletion, clonal VK1f/6-Kde recombinations were mainly identified. These rearrangements were quantified to follow-up seven B-ALL after induction using patient-specific ASO. Four patients had an undetectable level of MRD with a sensitivity of up to 10-5. This molecular approach allowed identification of prognosis risk group and adequate therapeutic decision. The IGK-Kde and IGH gene rearrangements might be used for diagnosis and MRD monitoring of B-ALL, introduced for the first time in Tunisian laboratories.

Molecular characterization of a Tunisian B-lineage leukemia using Kde gene rearrangements

“…In other study, we performed real time quantitative PCR using allele-specific oligonucleotide targeting N-region in B-ALL cases, and prominent results were obtained for MRD monitoring. 21 Further investigation on B-CLL are needed. Nowadays serval markers have been performed for MRD assessing, such as IKZF1 deletions or NOTCH1/FBXW7 mutations but Kde rearrangement remain a valuable tools in case of absence of mutations or deletions.…”

Risk Factors for Relapse of Childhood B Cell Acute Lymphoblastic Leukemia

“…With the use of multi-agent chemotherapy strategies, the long-term clinical outcomes of childhood ALL patients have been significantly improved, with an overall survival (OS) rate more than 90% [ 3 ]. B cell acute lymphoblastic leukemia (B-ALL) is the most common type of ALL, accounting more than 70% of cases [ 4 ]. However, due to the medical discrepancies among different regions and hospitals in China, the cure rate of ALL is significantly lower than in Europe and the USA [ 5 ].…”

Detection of IG and TCR Monoclonality as a Molecular Marker in Acute Hematopathies

“…Acute lymphoblastic leukemia (ALL) includes a heterogeneous group of malignant disorders which originate from different significant genetic lesions in B and T progenitor cells, including mutations that lead to phasespecific developmental arrest and interfere with the ability of self-renewal, resulting in clonal expansion of immature progenitor cells [1]. Presently, discriminating between reactive processes and malignant lymphoid proliferations implies a combination of clinical aspects, immunophenotype, cyto/histomorphology and detection of chromosomal abnormalities.…”