Fusion gene transcripts and Ig/TCR gene rearrangements are complementary but infrequent targets for PCR-based detection of minimal residual disease in acute myeloid leukemia

Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol

“…Although MRD levels in PB do not reflect MRD levels in BM, MRD information from PB samples still may have prognostic significance. 13,[24][25][26] However, we found no prognostic significance for PB MRD at TP2 with no difference in levels between patients who remained in remission and those who relapsed (data not shown).…”

Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement

“…Interestingly, oligoclonality and ongoing rearrangements of IGH and TCRD genes both correlated with higher transcriptional RAG1/2 levels, which were significantly higher in the entire infant ALL group as compared to childhood ALL. 40 This would fit with the immaturity of infant ALL as RAG1/2 levels during normal B-cell development are highest during DH-JH and VH-DH-JH gene rearrangements. 43 It has previously been shown that CD34 positivity was more common in MLL-AF4-positive ALL cases compared to E2A-PBX1-positive ALL cases, also supporting the immaturity of the malignant MLL-AF4-positive cell.…”

“…The mean transcription levels of RAG1 and RAG2 in infant ALL cases (n ¼ 42) were 3.2 and 14.0, respectively, which is much higher than previously determined RAG1/RAG2 levels of 0.1 and 0.2, respectively, in childhood ALL cases (Mann-Whitney U-test, Po0.001). 40 The level of RAG1 expression correlated with the total number of rearrangements at TCRD locus (r s ¼ 0.35, P ¼ 0.024) as well as the total number of TCR gene rearrangements (r s ¼ 0.33, P ¼ 0.032), but not with the total number of rearrangements at IGH, IGK, IGL, TCRB, TCRG loci or the total number of Ig gene rearrangements. In addition, the level of RAG2 expression was significantly higher in patients with oligoclonality at the IGH locus as compared to monoclonal patients (Mann-Whitney U-test, P ¼ 0.010).…”

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.…”

“…[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. 15,27,28 In addition to these crosslineage rearrangements, it has been established that several lymphoid malignancies have unusual Ig/ TCR gene rearrangement patterns.…”