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

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.

[1]  A. Zelenetz,et al.  Acute lymphoblastic leukemia. , 2019, Journal of the National Comprehensive Cancer Network : JNCCN.

[2]  D. Parkin,et al.  Trends in the incidence of cancer in the Sousse region, Tunisia, 1993–2006 , 2010, International journal of cancer.

[3]  R. Hafsia,et al.  Suivi de la maladie résiduelle dans les leucémies aiguës par cytométrie en flux , 2009 .

[4]  T. Révész,et al.  Sensitive and specific measurement of minimal residual disease in acute lymphoblastic leukemia. , 2009, The Journal of molecular diagnostics : JMD.

[5]  J. Wachowiak,et al.  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 , 2008, Archivum Immunologiae et Therapiae Experimentalis.

[6]  M. Lefranc,et al.  Chemiluminescent detection of clonal immunoglobulin and T cell receptor gene rearrangements in Tunisian lymphoid malignancies, leukemias and lymphomas , 2006, Leukemia & lymphoma.

[7]  B. Nadel,et al.  Unraveling the Consecutive Recombination Events in the Human IGK Locus1 , 2004, The Journal of Immunology.

[8]  Marie-Paule Lefranc,et al.  IMGT/V-QUEST, an integrated software program for immunoglobulin and T cell receptor VJ and VDJrearrangement analysis , 2004, Nucleic Acids Res..

[9]  M Hummel,et al.  Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936 , 2003, Leukemia.

[10]  J. Gabert,et al.  Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects , 2003, Leukemia.

[11]  C. V. D. Schoot,et al.  Immunoglobulin kappa deleting element rearrangements in precursor-B acute lymphoblastic leukemia are stable targets for detection of minimal residual disease by real-time quantitative PCR , 2002, Leukemia.

[12]  C. Scrideli,et al.  Minimal residual disease in Brazilian children with acute lymphoid leukemia: comparison of three detection methods by PCR. , 2002, Leukemia research.

[13]  K. Rajewsky,et al.  Regulation of immunoglobulin light chain gene rearrangements during early B cell development in the human , 2001, European journal of immunology.

[14]  L. Foroni,et al.  Immunoglobulin heavy-chain gene rearrangement in adult acute lymphoblastic leukemia reveals preferential usage of J(H)-proximal variable gene segments. , 2001, Blood.

[15]  C. V. D. Schoot,et al.  Application of germline IGH probes in real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia , 2000, Leukemia.

[16]  M. Andreeff,et al.  Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  S. Panzer,et al.  Multiplex PCR reaction for the detection and identification of immunoglobulin kappa deleting element rearrangements in B‐lineage leukaemias , 1999, British Journal of Haematology.

[18]  T. Szczepański,et al.  Cross-lineage T cell receptor gene rearrangements occur in more than ninety percent of childhood precursor-B acute lymphoblastic leukemias: alternative PCR targets for detection of minimal residual disease , 1999, Leukemia.

[19]  M. Kami,et al.  Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood , 1998, The Lancet.

[20]  W. Hop,et al.  Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood , 1998, The Lancet.

[21]  M. Stul,et al.  Immunoglobulin and T cell receptor gene rearrangement patterns in acute lymphoblastic leukemia are less mature in adults than in children: implications for selection of PCR targets for detection of minimal residual disease , 1998, Leukemia.

[22]  A Orfao,et al.  Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). , 1995, Leukemia.

[23]  J. V. van Dongen,et al.  Detection of immunoglobulin kappa light-chain gene rearrangement patterns by Southern blot analysis. , 1994, Leukemia.

[24]  K. Rajewsky,et al.  Detection of clonal B cell populations in paraffin-embedded tissues by polymerase chain reaction. , 1993, The American journal of pathology.

[25]  J. V. van Dongen,et al.  Analysis of immunoglobulin and T cell receptor genes. Part I: Basic and technical aspects. , 1991, Clinica chimica acta; international journal of clinical chemistry.

[26]  J. Norton,et al.  Immunoglobulin gene ‘fingerprinting’: an approach to analysis of B lymphoid clonality in lymphoproliferative disorders , 1991, British journal of haematology.

[27]  K. Siminovitch,et al.  The human kappa deleting element and the mouse recombining segment share DNA sequence homology. , 1987, Nucleic acids research.

[28]  G Flandrin,et al.  Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. , 1985, Annals of internal medicine.

[29]  C. Bartram,et al.  Duplex PCR facilitates the identification of immunoglobulin kappa (IGK) gene rearrangements in acute lymphoblastic leukemia , 2000, Leukemia.

[30]  I. Tomlinson,et al.  The human immunoglobulin VH repertoire. , 1995, Immunology today.

[31]  M. Lefranc,et al.  First study of immunoglobulin and T cell receptor gene rearrangements in chronic and acute lymphoblastic leukemias from Tunisia. , 1995, Experimental and clinical immunogenetics.

[32]  S. Korsmeyer,et al.  A uniform deleting element mediates the loss of kappa genes in human B cells. , 1985, Nature.