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

Abstract

The discrepancies could be assigned to the presence of 'atypical' TCRD gene rearrangements or translocations only detectable by SB, but also to efficient PCR-based detection of rearrangements derived from small subclones, which are difficult to detect with SB. Indications for oligoclonality were observed in 38% and 30% of patients with TCRG and TCRD gene rearrangements, respectively, which is comparable to the frequency of oligoclonality in IGH locus. Based on the combined data it was possible to reduce the broad panel of six TCRD and 12 TCRG primer combinations for MRD studies to two TCRD combinations (V␦2-D␦3 and D␦2-D␦3) and six TCRG combinations (V␥I, V␥II, V␥IV family-specific primers with J␥1.1/2.1 and J␥1.3/2.3 primers) resulting in the detection of 80% and 97% of all TCRD and TCRG gene rearrangements, respectively. Finally, the heteroduplex PCR data indicate that MRD monitoring with TCRG and/or TCRD targets is possible in approximately 80% of childhood precursor-B-ALL patients; ෂ55% of patients even have two TCRG and/or TCRD targets.

Biochemical and Folding Defects in a RAG1 Variant Associated with Omenn Syndrome

“…This suggests that a higher level of recombinase activity is required to support Ig gene rearrangement. In agreement with this, the level of recombinase activity present in recombining pro-/pre-B lymphocytes appears to be higher than that in pro-/pre-T lymphocytes (40,41). Finally, we cannot rule out the possibility of secondary, compensatory mutations in the T cell population, as has been observed in at least one other OS case (17).…”

Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936

“…28 TCRB rearrangements are not restricted to T-lineage malignancies as about one-third of precursor B-ALL harbor rearranged TCRB genes. 30 Their frequency is much lower (0-7%) in mature B-cell proliferations. 21 The human TCRB locus is located on the long arm of chromosome 7, at band 7q34 and spans a region of 685 kb.…”

“…Ig and TCR gene rearrangements are not markers for lineage: In contrast to the initial assumption, it has now been clear for more than a decade that Ig and TCR gene rearrangements are not necessarily restricted to B-and T-cell lineages, respectively. Crosslineage TCR gene rearrangements occur relatively frequently in immature B-cell malignancies, particularly in precursor B-ALL (490% of cases), 30 but also acute myeloid leukemias (AMLs) and mature B-cell malignancies might contain TCR gene rearrangements. [31][32][33] Crosslineage Ig gene rearrangements, mainly involving the IGH locus, also occur in T-cell malignancies and AML, albeit at a lower frequency.…”

Cutting Edge: TCR δ Gene Is Frequently Rearranged in Adult B Lymphocytes

“…Conversely, malignant B cell precursors contain cross-lineage TCR gene rearrangement in over 90% of children with precursor B acute lymphoblastic leukemia (ALL) (5). In leukemias, the most frequent among the known cross-lineage TCR gene rearrangements are V␦2-D␦3 and D␦2-D␦3 of the TCR ␦ gene locus, which physiologically codes for TCR ␦-chain (5).…”