Implementation of the standard strategy for identification of Ig/TCR targets for minimal residual disease diagnostics in B-cell precursor ALL pediatric patients: Polish experience

• Authors: M. Dawidowska , J. Jolkowska , T. Szczepanski , K. Derwich , J. Wachowiak , M. Witt
• Languages of publication: EN

Abstracts

EN

Introduction: Minimal residual disease (MRD), detected based on immunoglobulin and T-cell receptor (Ig/TCR) gene rearrangements as markers of residual leukemic cells, is currently the most reliable prognostic factor in acute lymphoblastic leukemia (ALL). A feasibility study is presented of the standard strategy for the identification of Ig/TCR targets for MRD diagnostics in Polish ALL patients by identifying Ig/TCR gene rearrangement pattern using standard primer sets and protocols. Materials and Methods: The PCR-heteroduplex approach based on BIOMED-1 and BIOMED-2 protocols (recommended as the European standard) was used to detect IGH, IGK-Kde, TCRD, TCRG, and TCRB rearrangements in 58 Polish B-cell precursor ALL patients. Sequencing and homology analysis between the obtained and germline Ig/TCR sequences enabled identification of the rearrangements.The U-Gauss test was used for statistical analysis of the Ig/TCR rearrangement pattern in Polish patients compared with relevant data on other nationalities. Results: The following pattern was identified: IGH: 83% (VH-JH: 74%, DH-JH: 9%), IGK-Kde: 41%, TCRD: 78% (incomplete TCRD: 55%, Vdelta2-Ddelta3: 45%, Ddelta2-Ddelta3: 21%, Vdelta2-Jalpha: 35%), TCRG: 50%, and TCRB: 13%. Considerable convergence of the Ig/TCR pattern in Polish patients and those of other nationalities (mainly West Europeans) was demonstrated. Statistically relevant differences were only found between the incidence of DH-JH in Polish (9%) and Dutch patients (24%; p<0.05) and Polish and Italian patients (19%; p<0.05), VH-JH in Polish (74%) and Chilean patients (100%; p<0.05), and TCRG in Polish (50%) and Brazilian patients (69%; p<0.05). Conclusions: The convergence of Ig/TCR patterns in Polish and European patients indicates that the strategy for Ig/TCR target identification based on standard primers and protocols might be directly used for the construction of Polish standards and recommendations for MRD diagnostics.

Keywords

EN

ACUTE LYMPHOBLASTIC LEUKEMIA; GENE REARRANGEMENT; RESIDUAL DISEASE

Discipline

• IMMUNOLOGY: IMMUNOLOGY

• Publisher: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences
• Journal: Archivum Immunologiae et Therapiae Experimentalis
• Year: 2008
• Volume: 56
• Issue: 6
• Pages: 409-418

Contributors

author

M. Dawidowska

author

J. Jolkowska

author

T. Szczepanski

author

K. Derwich

author

J. Wachowiak

author

M. Witt

• Document Type: ARTICLE
• Publication order reference: Malgorzata Dawidowska, Department of Molecular and Clinical Genetics, Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, Poland