Precursor-B-ALL with D(H)-J(H) gene rearrangements have an immature immunogenotype with a high frequency of oligoclonality and hyperdiploidy of chromosome 14
- PMID: 11516102
- DOI: 10.1038/sj.leu.2402206
Precursor-B-ALL with D(H)-J(H) gene rearrangements have an immature immunogenotype with a high frequency of oligoclonality and hyperdiploidy of chromosome 14
Abstract
The IGH gene configuration was investigated in 97 childhood precursor-B-ALL patients at initial diagnosis. Rearrangements were found by Southern blotting in all but three patients (97%) and in 30 cases (31%) we observed oligoclonal IGH gene rearrangements. Heteroduplex PCR analysis revealed at least one clonal PCR product in all Southern blot-positive cases. In 89 patients (92%) complete V(D)J rearrangements were found, while incomplete D(H)-J(H) rearrangements occurred in only 21 patients (22%). In 5% of cases the D(H)-J(H) rearrangements were the sole IGH gene rearrangements. Sequence analysis of the 31 identified incomplete rearrangements revealed preferential usage of segments from the D(H)2, D(H)3 and D(H)7 families (78%). While D(H)2 and D(H)3 gene rearrangements occur frequently in normal B cells and B cell precursors, the relatively frequent usage of D(H)7-27 (19%) in precursor-B-ALL patients is suggestive of leukemic transformation during prenatal lymphopoiesis. Among J(H) gene segments in the incomplete D(H)-J(H) rearrangements, the J(H)6 segment was significantly overrepresented (61%). This observation together with the predominant usage of the most upstream D(H) genes indicates that many of the identified clonal D(H)-J(H) gene rearrangements in precursor-B-ALL probably represent secondary recombinations, having deleted pre-existing D(H)-J(H) joinings. The patients with incomplete D(H)-J(H) gene rearrangements were frequently characterized by hyperdiploid karyotype with additional copies of chromosome 14 and/or by IGH oligoclonality. The presence of incomplete D(H)-J(H) joinings was also significantly associated with a less mature immunogenotype: overrepresentation of V(H)6-1 gene segment usage, absence of biallelic TCRD deletions, and low frequency of TCRG gene rearrangements. This immature immunogenotype of precursor-B-ALL with incomplete IGH gene rearrangements was not associated with more aggressive disease.
Similar articles
-
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.Leukemia. 1999 Feb;13(2):196-205. doi: 10.1038/sj.leu.2401277. Leukemia. 1999. PMID: 10025893 Clinical Trial.
-
Age-related patterns of immunoglobulin and T-cell receptor gene rearrangements in precursor-B-ALL: implications for detection of minimal residual disease.Leukemia. 2003 Sep;17(9):1834-44. doi: 10.1038/sj.leu.2403038. Leukemia. 2003. PMID: 12970784
-
Ig heavy chain gene rearrangements in T-cell acute lymphoblastic leukemia exhibit predominant DH6-19 and DH7-27 gene usage, can result in complete V-D-J rearrangements, and are rare in T-cell receptor alpha beta lineage.Blood. 1999 Jun 15;93(12):4079-85. Blood. 1999. PMID: 10361104
-
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.Leukemia. 1998 Jul;12(7):1081-8. doi: 10.1038/sj.leu.2401071. Leukemia. 1998. PMID: 9665194
-
[Analyses of the rearrangement of T-cell receptor- and immunoglobulin genes in the diagnosis of lymphoproliferative disorders].Veroff Pathol. 1995;144:1-109. Veroff Pathol. 1995. PMID: 7856305 Review. German.
Cited by
-
Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications.Front Immunol. 2023 Apr 18;14:1125017. doi: 10.3389/fimmu.2023.1125017. eCollection 2023. Front Immunol. 2023. PMID: 37143651 Free PMC article.
-
Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia.Nat Commun. 2023 Mar 25;14(1):1658. doi: 10.1038/s41467-023-37356-5. Nat Commun. 2023. PMID: 36966135 Free PMC article.
-
Somatic Sex: On the Origin of Neoplasms With Chromosome Counts in Uneven Ploidy Ranges.Front Cell Dev Biol. 2021 Aug 4;9:631946. doi: 10.3389/fcell.2021.631946. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 34422788 Free PMC article.
-
Regulation of shrimp prophenoloxidase activating system by lva-miR-4850 during bacterial infection.Sci Rep. 2021 Feb 15;11(1):3821. doi: 10.1038/s41598-021-82881-2. Sci Rep. 2021. PMID: 33589707 Free PMC article.
-
Sister chromatid cohesion defects are associated with chromosomal copy number heterogeneity in high hyperdiploid childhood acute lymphoblastic leukemia.Genes Chromosomes Cancer. 2021 Jun;60(6):410-417. doi: 10.1002/gcc.22933. Epub 2021 Jan 16. Genes Chromosomes Cancer. 2021. PMID: 33368842 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources