Immunoglobulin κ gene rearrangements between the κ deleting element and Jκ recombination signal sequences in acute lymphoblastic leukemia and normal hematopoiesis

Seriu, Taku; Hansen-Hagge, TE; Stark, Yvonne; Bartram, CR

doi:10.1038/sj.leu.2401745

Cited by 16 publications

(10 citation statements)

References 19 publications

(20 reference statements)

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“…This complex rearrangement can only be explained by a multistep process. 32 Irrespective of the subclonal origin of the four TCRG gene rearrangements in the random series of 95 AML patients, it is remarkable that the Only reports on large patient series (n Ͼ 50) were used for this Table. NT, not tested.…”

Section: Leukemiamentioning

confidence: 99%

Fusion gene transcripts and Ig/TCR gene rearrangements are complementary but infrequent targets for PCR-based detection of minimal residual disease in acute myeloid leukemia

et al. 2002

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Section: Leukemiamentioning

confidence: 99%

Fusion gene transcripts and Ig/TCR gene rearrangements are complementary but infrequent targets for PCR-based detection of minimal residual disease in acute myeloid leukemia

et al. 2002

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“…Analysis of Igk in conjunction with IgH rearrangements substantially improves the detection of lymphoid clonality in B-cell neoplasms. 12,13 The relatively insensitive Southern blot technique has been used to study the involvement of peripheral blood or bone marrow in a variety of NHL subtypes. 14,15 However, there are no large clinical studies evaluating the use of PCR staging in DLBCL.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of molecular staging by PCR-amplification of immunoglobulin gene rearrangements in diffuse large B-cell lymphoma (DLBCL)

Mitterbauer-Hohendanner

Mannhalter

Winkler

et al. 2004

Leukemia

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The prognostic value of the detection of peripheral blood (PB) and/or bone marrow (BM) involvement by polymerase chain reaction (PCR) amplification of rearranged immunoglobulin heavy chain (IgH) and immunoglobulin kappa light chain (Igj) genes was evaluated in 155 patients with diffuse large B-cell lymphomas (DLBCL). Immunoglobulin gene rearrangements (IgR) were detected in 35/155 (23%) patients. The presence of IgR in PB/BM was related to clinical stage (CS I-III vs CS IV; Po0.001), histopathological detection of BM involvement (Po0.001), and the International Prognostic Index (Po0.001). IgR-positive cases had a significantly lower complete remission (CR) rate (18/35, 51%) than IgR-negative patients (85/120, 71%; P ¼ 0.042), and a significantly poorer overall survival (OAS) at 5 years (25 vs 66%; Po0.001). There was a significant difference in the estimated OAS at 5 years between patients with negative BM histology and negative PCR results (66%), patients with negative BM histology but positive IgR (37%), and patients with positive BM histology (12%). Our results indicate that molecular methods improve the accuracy of staging in patients with DLBCL and define a group of patients with normal bone marrow histology who have a significantly poorer OAS due to molecular detection of PB/BM involvement.

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“…as an intermediate step in the V(D)J-mediated oncogenic rearrangement in t (7,9) in T-ALL (26). In thymocytes of healthy individuals, a signal joint configuration between the D␤1RSS and a fortuitous RSS in the TAL2 locus on chromosome 9 can occasionally be observed as a result of V(D)J-mediated translocation.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, JRSS-Kde rearrangements have been identified in a case of human acute leukemia (9). The effects of these so-called atypical IGK rearrangements are versatile.…”

mentioning

confidence: 99%

Unraveling the Consecutive Recombination Events in the HumanIGKLocus

Langerak

Nadel

Torbal

et al. 2004

The Journal of Immunology

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In addition to the classical Vκ-Jκ, Vκ-κ deleting element (Kde), and intron-Kde gene rearrangements, atypical recombinations involving Jκ recombination signal sequence (RSS) or intronRSS elements can occur in the Igκ (IGK) locus, as observed in human B cell malignancies. In-depth analysis revealed that atypical JκRSS-intronRSS, Vκ-intronRSS, and JκRSS-Kde recombinations not only occur in B cell malignancies, but rather reflect physiological gene rearrangements present in normal human B cells as well. Excision circle analysis and recombination substrate assays can discriminate between single-step vs multistep rearrangements. Using this combined approach, we unraveled that the atypical Vκ-intronRSS and JκRSS-Kde pseudohybrid joints most probably result from ongoing recombination following an initial aberrant JκRSS-intronRSS signal joint formation. Based on our observations in normal and malignant human B cells, a model is presented to describe the sequential (classical and atypical) recombination events in the human IGK locus and their estimated relative frequencies (0.2–1.0 vs <0.03). The initial JκRSS-intronRSS signal joint formation (except for Jκ1RSS-intronRSS) might be a side event of an active V(D)J recombination mechanism, but the subsequent formation of Vκ-intronRSS and JκRSS-Kde pseudohybrid joints can represent an alternative pathway for IGK allele inactivation and allelic exclusion, in addition to classical Cκ deletions. Although usage of this alternative pathway is limited, it seems essential for inactivation of those IGK alleles that have undergone initial aberrant recombinations, which might otherwise hamper selection of functional Ig L chain proteins.

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Immunoglobulin κ gene rearrangements between the κ deleting element and Jκ recombination signal sequences in acute lymphoblastic leukemia and normal hematopoiesis

Cited by 16 publications

References 19 publications

Fusion gene transcripts and Ig/TCR gene rearrangements are complementary but infrequent targets for PCR-based detection of minimal residual disease in acute myeloid leukemia

Fusion gene transcripts and Ig/TCR gene rearrangements are complementary but infrequent targets for PCR-based detection of minimal residual disease in acute myeloid leukemia

Prognostic significance of molecular staging by PCR-amplification of immunoglobulin gene rearrangements in diffuse large B-cell lymphoma (DLBCL)

Unraveling the Consecutive Recombination Events in the HumanIGKLocus

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