Continuing rearrangement but absence of somatic hypermutation in immunoglobulin genes of human B cell precursor leukemia.

Abstract

Southern blot analyses revealed that cells from nearly 30% of childhood B cell precursor acute lymphoblastic leukemias (ALLs) contained more than two rearranged, nongermline bands for Ig heavy chain genes. DNA corresponding to these bands was molecularly cloned from two cases which showed three and seven rearranged bands, respectively. Nucleotide sequence analysis of the cloned DNA demonstrated that each band represented different VDJ or DJ rearrangements. While the same DJ joints were shared by several rearrangements, different DJ joints were found in the majority of rearrangements, precluding V region substitution as an explanation for the multiplicity of heavy chain rearrangements in these leukemias. Most of the V region segments involved in these rearrangements were restricted to VH region families that have been shown previously to be preferentially rearranged in human fetal B lineage cells. Sequence analysis of multiple copies of the same VDJ rearrangements from different cells revealed no somatic mutation, a mechanism responsible for detection of extra rearranged Ig DNA bands in certain other B lineage tumors. The data suggest that in some cases of ALL Ig heavy chain genes begin and continue to rearrange de novo within the neoplastic B cell precursor populations derived from an original malignant cell transformed at a stem cell stage of differentiation.

Immunoglobulin lambda isotype gene rearrangements in B cell malignancies

“…19 This results in the occurrence of ongoing Ig gene rearrangements in 30 to 40% of cases and cross-lineage T cell receptor gene rearrangements in approximately 90% of cases. [20][21][22][23] Despite this continuous activity of the recombinase enzyme system, we observed only a low frequency of 20% IGL rearrangements. This might be caused by a lower accessibility of the IGL locus for recombination at this immature differentiation stage.…”

Histologic transformation of follicular lymphoma to diffuse lymphoma represents tumor progression by a single malignant B cell.

“…In FL, active somatic mutation is well described (36). In contrast, somatic mutation has not been observed in ALL, SNC-B, and small lymphocytic lymphoma, lymphoid malignancies representing other stages of B cell development (48)(49)(50)(51) . In DLCL it is not known if somatic mutation is ongoing.…”

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

“…5 However, the encountered high frequency of oligoclonal IGH rearrangement patterns at diagnosis together with the instability of the individual rearrangements at relapse has questioned its use as a clonal marker for MRD detection. [6][7][8][9][10][11][12][13][14][15] IGH genes are rearranged in an ordered fashion during lymphoid development starting with a DJ H rearrangement on both alleles. Then, a V H segment is joined to one of the DJ H rearrangements.…”