Molecular characterization of illegitimate TCRδ gene rearrangements in acute myeloid leukaemia

Abstract

Recently, we and others have shown the occurrence of TCR delta gene rearrangements in acute myeloid leukaemia (AML). In this study we describe the molecular characteristics of these rearrangements by the polymerase chain reaction (PCR) and the direct sequencing of PCR products. 11 rearrangements were characterized in blast cell samples from six patients. We found a heterogenous pattern of TCR delta gene rearrangements with involvement of V delta 1-5 regions. These findings differ from observations in T-ALL and B-cell precursor ALL, where predominantly usage of V delta 1 and V delta 2 regions has been described. Furthermore, extensive diversity of junctional sites was observed, including addition of up to 37 N nucleotides, nucleotide deletions at junction sites of V delta and J delta segments and usage of up to three D delta segments. The D delta 3 fragment was the most frequently used diversity element and was found in 10 rearrangements. Nine of the 11 rearrangements were non-functional, either incomplete or out of the reading frame. Therefore a functional TCR delta cannot be expressed in these myeloid blast cells.

Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL

“…[4][5][6] However, our results and the published data indicate that in about 20% of ALL, the rearrangements detected by SB cannot be amplified by PCR. [4][5][6] These atypical rearrangements might involve yet unknown TCRD recombinatorial elements or regions located outside the TCRD locus, or even on different chromosomes, resulting in chromosomal aberrations. Chromosomal translocations involving the TCRA/D locus on chromosome 14 and the TCRB locus on chromosome 7 are associated with T-ALL.…”

“…2,3 Owing to a limited number of gene segments, TCRD recombinations can be easily identified by Southern blot (SB) analysis and even more precisely by PCR. [4][5][6] However, our results and the published data indicate that in about 20% of ALL, the rearrangements detected by SB cannot be amplified by PCR. [4][5][6] These atypical rearrangements might involve yet unknown TCRD recombinatorial elements or regions located outside the TCRD locus, or even on different chromosomes, resulting in chromosomal aberrations.…”

Acute myeloid and T‐cell acute lymphoblastic leukaemia with aberrant antigen expression exhibit similar TCRδ gene rearrangements

“…Three AML cases were in part described previously (Przybylski et al, 1994). In this study 29 acute leukaemia cases exhibiting a TCR gene rearrangement by Southern blot analysis were investigated.…”

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

“…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. 33,34 Virtually all (498%) TCRab þ T-cell malignancies have TCRG gene rearrangements (generally biallelic) and many TCRgd þ Tcell malignancies have TCRB gene rearrangements, implying that the detection of TCRB or TCRG rearrangements is not indicative of T cells of the ab or gd T-cell lineage, respectively, either.…”