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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
Unexpected immunoglobulin light chain gene rearrangements in myeloid antigen positive acute lymphoid leukemia
E Paietta1, B Van Ness, J M Bennett
1Department of Oncology, Montefiore Medical Center, Bronx, NY 10467.
Blast cells from 10 immunologically diagnosed adult acute lymphoid leukemias expressing myeloid antigens (M+ALL) were studied for immunoglobulin heavy (IgH) and light chain as well as T-cell receptor (TCR)-beta chain gene rearrangements. All but one leukemic isolate met the FAB-criteria for ALL. DNA from 2 patients with pre-pre-B-ALL (CD10-) and 1 patient with common ALL contained rearranged Ig light chain (kappa in two, lambda in one case) in addition to rearranged IgH genes. The TCR-beta chain gene was germline in all pre-pre-B leukemias and rearranged in common ALLs (bigenotypic features). One patient with mature B-ALL showed IgH and light chain gene rearrangements. DNA from 2 pre-T-ALLs contained rearranged TCR-beta chain genes plus rearranged IgH genes in one case. Ig light chain gene rearrangements in immature M+ALL were not associated with gross chromosomal abnormalities except for one Philadelphia chromosome positive case. The occurrence of Ig light chain gene rearrangements in M+ALL with immature lymphoid immunophenotype might represent an hitherto unrecognized aberrant differentiation potential of transformed multipotential stem cells with commitment towards the lymphoid lineage.
Blast cells from 10 immunologically diagnosed adult acute lymphoid leukemias expressing myeloid antigens (M+ALL) were studied for immunoglobulin heavy (IgH) and light chain as well as T-cell receptor (TCR)-beta chain gene rearrangements. All but one leukemic isolate met the FAB-criteria for ALL. DNA from 2 patients with pre-pre-B-ALL (CD10-) and 1 patient with common ALL contained rearranged Ig light chain (kappa in two, lambda in one case) in addition to rearranged IgH genes. The TCR-beta chain gene was germline in all pre-pre-B leukemias and rearranged in common ALLs (bigenotypic features). One patient with mature B-ALL showed IgH and light chain gene rearrangements. DNA from 2 pre-T-ALLs contained rearranged TCR-beta chain genes plus rearranged IgH genes in one case. Ig light chain gene rearrangements in immature M+ALL were not associated with gross chromosomal abnormalities except for one Philadelphia chromosome positive case. The occurrence of Ig light chain gene rearrangements in M+ALL with immature lymphoid immunophenotype might represent an hitherto unrecognized aberrant differentiation potential of transformed multipotential stem cells with commitment towards the lymphoid lineage.

