Configuration of immunoglobulin and T cell receptor beta and gamma genes in acute myeloid leukaemia: pitfalls in the analysis of 40 cases.

Parreira, Leonor; Carvalho, Caroline; Moura, Hércules; Melo, Alanne Rayssa da Silva; Santos, Paula Segovia-de los; Guimaraes, JE; Parreira, A

doi:10.1136/jcp.45.3.193

Cited by 7 publications

(5 citation statements)

References 33 publications

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“…Although the recombinations of the TcR and the Ig genes are not lineage specific, this does not mean they are not of use in haematological diagnosis. These analyses are not informative in the study of B-lineage ALL because of their high frequency; however, the relatively low frequency of the recombinations of these genes as non-specific to the lineage in T-ALL and AML observed by us and other authors [16,17,20] indicates that this type of analysis could be a further parameter, together with the immunophenotype and morphology in the haematological diagnosis of indetermined or doubtful leukaemias. Two of the four AUL cases presented in the present study showed the TcR and the Igs genes in the germinal configuration.…”

Section: Discussionmentioning

confidence: 86%

T‐cell receptor gene rearrangements in lymphoid and non‐lymphoid leukaemias

Casares

Rodríguez

Martín

et al. 1994

Eur J Clin Investigation

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Rearrangements of delta-, tau-, and beta- T-cell receptor (TcR) chain genes were analysed in 64 haematologic malignancies comprising T- and B-lineage acute lymphoblastic leukaemias (ALL), B-chronic lymphocytic leukaemias (CLL), acute myeloid leukaemias (AML) and acute undifferentiated leukaemias AUL). The TcR genes were rearranged in 5/6 T-ALL. In non-T-leukaemias the frequency of TcR gene rearrangements was higher in B-lineage ALL (8/11), although they were all detected in B-CLL (5/29), AML (1/16) and AUL (2/4). Immunoglobulin (Ig) gene rearrangements were observed in 1/6 T-ALL and 2/14 AML. The analysis of these gene configurations has a diagnostic application since it allows the definition of the clonality of malignant proliferation and although they are not lineage specific such configurations represent a further parameter to evaluate, together with the immunophenotype and morphology, in the assignment or exclusion of the differentiation lineage of the haematologic malignancies.

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Section: Discussionmentioning

confidence: 86%

T‐cell receptor gene rearrangements in lymphoid and non‐lymphoid leukaemias

Casares

Rodríguez

Martín

et al. 1994

Eur J Clin Investigation

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“…While similarities between ETP T-ALL and AML have been previously recognized (Van Vlierberghe et al , 2011a; Zhang et al , 2012; Zuurbier et al , 2014), we propose that the biological overlap of AMTL is not with AML per se , but with a specific subset of AML cases that also exhibit T cell lymphoid features. Namely, a subset of AMLs has long been recognized to harbour clonal T-cell receptor (TCR) or immunoglobulin (Ig) gene rearrangements, indicating activity of the RAG recombinase that is responsible for generating somatic V(D)J recombination at these loci at specific stages of lymphoid development (Norton et al , 1987; Parreira et al , 1992; Schmidt et al , 1992). These AML cases can also express the lymphoid marker terminal deoxynucleotidyltransferase (TdT, also known as DNTT), which generates diversity at the TCR and Ig genes by mutating the junctions of rearrangements during V(D)J recombination (Drexler et al , 1993; Patel et al , 2013).…”

Section: Acute Myeloid/t-lymphoblastic Leukaemia (Amtl): Acute Leukaementioning

confidence: 99%

Acute myeloid/T‐lymphoblastic leukaemia (AMTL): a distinct category of acute leukaemias with common pathogenesis in need of improved therapy

Gutiérrez

Kentsis

2018

Br J Haematol

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Advances in the classification of acute leukaemias have led to improved outcomes for a substantial fraction of patients. However, chemotherapy resistance remains a major problem for specific subsets of acute leukaemias. Here, we propose that a molecularly distinct subtype of acute leukaemia with shared myeloid and T cell lymphoblastic features, which we term acute myeloid/T-lymphoblastic leukaemia (AMTL), is divided across 3 diagnostic categories owing to variable expression of markers deemed to be defining of myeloid and T-lymphoid lineages, such as myeloperoxidase and CD3. This proposed diagnostic group is supported by (i) retained myeloid differentiation potential during early T cell lymphoid development, (ii) recognition that some cases of acute myeloid leukaemia (AML) harbour hallmarks of T cell development, such as T-cell receptor gene rearrangements and (iii) common gene mutations in subsets of AML and T cell acute lymphoblastic leukaemia (T-ALL), including WT1, PHF6, RUNX1 and BCL11B. This proposed diagnostic entity overlaps with early T cell precursor (ETP) T-ALL and T cell/myeloid mixed phenotype acute leukaemias (MPALs), and also includes a subset of leukaemias currently classified as AML with features of T-lymphoblastic development. The proposed classification of AMTL as a distinct entity would enable more precise prospective diagnosis and permit the development of improved therapies for patients whose treatment is inadequate with current approaches.

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“…The presence of IgH gene rearrangements in approximately 10% of human AMLs [39][40][41][42][43][44] has been attributed to either lineage infidelity, involving an aberrant differentiation program in the leukemic cell, or lineage promiscuity of a lympho-myeloid progenitor cell and the corresponding leukemia. 14,43 Pre-B progenitor cells that can undergo myeloid differentiation under specific conditions have been detected in vitro, 45,46 supporting evidence for the lineage promiscuity model.…”

Section: Discussionmentioning

confidence: 99%

Allelic loss on chromosome 4 (Lyr2/TLSR5) is associated with myeloid, B–lympho-myeloid, and lymphoid (B and T) mouse radiation-induced leukemias

Cleary

Boulton

Plumb

2001

Blood

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The CBA/H mouse model of radiationinduced acute myeloid leukemia (AML) was re-examined using molecular approaches. In addition to the typical promyelocytic AMLs, 34% were reclassified as early pre-B lympho-myeloid leukemias (L-ML) based on leukemic blood cell morphology, immunoglobulin heavy-chain gene re-arrangements (IgH R ), or expression of both lymphoid (Vpre-B1 and Rag1) and myeloid (myeloperoxidase and lysozyme M) genes. Allelic loss on chromosome 4 was frequently detected in AMLs (53%) and L-MLs (more than 95%), and the preferential loss of the maternally transmitted allele suggests the locus may be imprinted. A minimally deleted region (MDR) maps to a 3.4-cM interval, which is frequently deleted in radiation-induced thymic lymphomas (TLSR5) and contains a recessive, maternally transmitted genetic locus (Lyr 2) that confers resistance to spontaneous and radiation-induced pre-B and T cell lymphomas, suggesting they are one and the same. Thus, the Lyr 2/TLSR5 locus is frequently implicated in myeloid, lymphoid (B and T), and mixed-lineage mouse leukemias and lymphomas. Epigenetic inactivation of one Lyr2/TLSR5 allele during normal mouse development suggests that only a single hit is required for its inactivation during leukemogenesis, and this may be a significant contributing factor to the efficiency of the leukemogenic process in the mouse. (Blood. 2001;98:1549-1554)

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Configuration of immunoglobulin and T cell receptor beta and gamma genes in acute myeloid leukaemia: pitfalls in the analysis of 40 cases.

Cited by 7 publications

References 33 publications

T‐cell receptor gene rearrangements in lymphoid and non‐lymphoid leukaemias

T‐cell receptor gene rearrangements in lymphoid and non‐lymphoid leukaemias

Acute myeloid/T‐lymphoblastic leukaemia (AMTL): a distinct category of acute leukaemias with common pathogenesis in need of improved therapy

Allelic loss on chromosome 4 (Lyr2/TLSR5) is associated with myeloid, B–lympho-myeloid, and lymphoid (B and T) mouse radiation-induced leukemias

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