Rearrangement status of the malignant cell determines type of secondary IgH rearrangement (V-replacement or V to DJ joining) in childhood B precursor acute lymphoblastic leukemia

Steenbergen, Eric J.; Verhagen, O. J. H. M.; Berg, Henk van den; Leeuwen, E. F. Van; Behrendt, H.; Slater, R.; Borne, A. E. G. K. Von Dem; Schoot, C. Ellen van der

doi:10.1038/sj.leu.2400720

Cited by 35 publications

(41 citation statements)

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“…29 Thus, the high frequency of V H (or D H ) to DJ H joins in HeH leukemias concords with their immature immunogenotype, 11,29 whereas TEL-AML1 positive cases more frequently had V H replacements as secondary rearrangements, which implies that the translocation had occurred in a more advanced cell. This assumption is supported by earlier observations on V H replacements at relapse occasions.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, the cases compiled in the heterogeneous group of the remaining BCP ALL seem, because of their predominant V H replacements, to originate from a more differentiated BCP. 10,29 Based on the reported high frequency of IGH oligoclonality by SB in BCP ALL of 30-40%, 32,33 which exceeds the overall frequency of oligoclonality in this study, we compared the results obtained with PCR and SB methods in HeH leukemias. Although the frequency of monoclonality or oligoclonality based on the two different verification techniques was highly concordant, the accordance rate for individual cases was only moderate.…”

Section: Discussionmentioning

confidence: 99%

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Chromosome 14 copy number-dependent IGH gene rearrangement patterns in high hyperdiploid childhood B-cell precursor ALL: implications for leukemia biology and minimal residual disease analysis

et al. 2009

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Childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL) is generally a clonal disease in which the number of IGH rearrangements per cell does not exceed the number of the IGH alleles on chromosome 14. Consequently, monoclonal high hyperdiploid (HeH) cases with a trisomy 14 can harbor three rearrangements, a pattern that otherwise may be misinterpreted to be oligoclonal. Oligoclonal IGH rearrangements, on the other hand, may be instable at relapse and should therefore not be used for minimal residual disease analysis. We thus investigated the association between IGH allele copy numbers and the IGH rearrangement patterns in 90 HeH BCP ALL with either two (13%) or three copies (87%) of chromosome 14. HeH cases (44%) had an oligoclonal IGH rearrangement pattern, but true oligoclonalityFafter correction for the respective copy number of IGH allelesFwas only 16%. Monoclonal and oligoclonal HeH cases had predominantly V H to preexisting DJ H recombinations, a finding that contrasts with oligoclonal cases of other major genetic BCP ALL subgroups in which V H replacements prevail. We conclude that for the precise assessment and correct interpretation of clonality patterns in BCP ALL, the IGH allele copy number has to be taken into consideration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chromosome 14 copy number-dependent IGH gene rearrangement patterns in high hyperdiploid childhood B-cell precursor ALL: implications for leukemia biology and minimal residual disease analysis

et al. 2009

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“…Single unproductive rearrangements are found at a measurable frequency in precursor B-cell neoplasms, for example, B-cell precursor acute lymphoblastic leukemia. 9 In contrast, they are very rare in malignancies of mature B cells, as the surface expression of the B-cell receptor is thought to be absolutely necessary for its survival through a tonic signaling within the cell. Therefore, the biological mechanisms that allow clonogenic progenitors lacking functional B-cell receptors to evade apoptosis are largely unknown.…”

Section: Explanationmentioning

confidence: 99%

Immunoglobulin sequence analysis and prognostication in CLL: guidelines from the ERIC review board for reliable interpretation of problematic cases

et al. 2011

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Immunoglobulin gene sequence analysis is widely utilized for prognostication in chronic lymphocytic leukemia (CLL) and the definition of standardized procedures has allowed reliable and reproducible results. Occasionally, a straightforward interpretation of the sequences is not possible because of the so-called 'problematic sequences' that do not fit the 'classic' interpretation and pose scientific questions at the cross-road between hematology and immunology. Thanks to a dedicated effort within the European Research Initiative on CLL (ERIC), we have now the possibility to present such cases, offer a scientific explanation and propose recommendations in terms of prognostication.

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“…Further, there may be occasional false-negative findings by flow cytometry due to immunophenotypic changes during therapy, 2,35 and by PCR due to oligoclonality at diagnosis and/or clonal evolution during the course of the disease. [36][37][38][39][40][41] The use of the two methods in tandem should offset the possibility of false-negative MRD results due to these events. …”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of flow cytometry and polymerase chain reaction for the detection of minimal residual disease in childhood acute lymphoblastic leukemia

et al. 2004

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Minimal residual disease (MRD) is an independent prognostic factor in childhood acute lymphoblastic leukemia (ALL). The most widely applied MRD assays in ALL are flow cytometric identification of leukemia immunophenotypes and polymerase chain reaction (PCR) amplification of antigen-receptor genes. We measured MRD by both assays in 227 patients with childhood B-lineage ALL. Of 1375 samples (736 bone marrow and 639 peripheral blood) examined, MRD was o0.01% in 1200, and X0.01% in 129 by both assays; MRD levels measured by the two methods correlated well. Of the remaining 46 samples, 28 had MRD X0.01% by flow cytometry but o0.01% by PCR. However, PCR (which had a consistent sensitivity of 0.001%) detected leukemic gene rearrangements in 26 of these 28 samples. Conversely, in 18 samples, MRD was X0.01% by PCR but o0.01% by flow cytometry. In nine of these samples, flow cytometry had a sensitivity of 0.001%, and detected aberrant immunophenotypes in eight samples. Therefore, the two most widely used methods for MRD detection in ALL yield concordant results in the vast majority of cases, although the estimated levels of MRD may vary in some. The use of the two methods in tandem ensures MRD monitoring in all patients.

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Rearrangement status of the malignant cell determines type of secondary IgH rearrangement (V-replacement or V to DJ joining) in childhood B precursor acute lymphoblastic leukemia

Abstract: Immunoglobulin heavy chain (IgH) oligoclonality in childhoodrearrangement occurs in each patient and that the type

Cited by 35 publications

References 4 publications

Chromosome 14 copy number-dependent IGH gene rearrangement patterns in high hyperdiploid childhood B-cell precursor ALL: implications for leukemia biology and minimal residual disease analysis

Chromosome 14 copy number-dependent IGH gene rearrangement patterns in high hyperdiploid childhood B-cell precursor ALL: implications for leukemia biology and minimal residual disease analysis

Immunoglobulin sequence analysis and prognostication in CLL: guidelines from the ERIC review board for reliable interpretation of problematic cases

Comparative analysis of flow cytometry and polymerase chain reaction for the detection of minimal residual disease in childhood acute lymphoblastic leukemia

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