Acute myeloid and T-cell acute lymphoblastic leukaemia with aberrant antigen expression exhibit similar TCRdelta gene rearrangements.
TCR delta gene recombination patterns were analysed by Southern blot, polymerase chain reaction and nucleotide sequencing in acute myeloid leukaemias, with coexpression of lymphoid antigens (Ly+ AML, n=10) as well as in early T-cell acute lymphoblastic leukaemias with (My+ T-ALL, n=10) and without coexpression of myeloid antigens (My(-) T-ALL, n=9). These 29 acute leukaemias exhibiting TCR delta gene rearrangements were selected from 66 Ly+ AML, 14 My+ T-ALL and 12 My(-) T-ALL cases. Similar recombination patterns, namely D delta 2J delta1 and V delta 1J delta1 gene rearrangements, were observed in Ly+ AML and My+T-ALL. In contrast to V delta2 D delta3 rearrangements in B-cell precursor ALL, these rearrangements require activation of a T-cell-specific TCR delta enhancer. Comparison of My+ T-ALL and Ly+ AML with My(-) T-ALL exhibited a higher incidence of incomplete D delta 2J delta1 rearrangements in My+ T-ALL and Ly+ AML. Since a D delta 2J delta1 rearrangement is an early event in TCR delta recombination, these leukaemias seem to be arrested at an earlier stage of differentiation. Similar patterns of TCR delta rearrangements in My+ T-ALL and Ly+ AML suggest existence of a common myeloid/T-lymphoid progenitor cell. Although weak or missing expression of terminal deoxynucleotidyl transferase (T delta T) was found in 7/10 Ly+ AML cases, no difference was observed in numbers of N-nucleotides inserted in junctional regions when comparing with 3/10 cases exhibiting TdT expression. Since TdT activity is necessary for N-nucleotide addition, this finding suggests down-regulation of T delta T expression after rearrangement took place in these Ly+ AML cases.
Schmidt
C A
CA
Virchow Klinikum, Abt. Hämatologie und Onkologie, Humboldt Universität Berlin, Germany.
Przybylski
G
G
Tietze
A
A
Oettle
H
H
Siegert
W
W
Ludwig
W D
WD
D000208:Acute Disease; D001483:Base Sequence; D015139:Blotting, Southern; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000276:immunology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D017421:Sequence Analysis
D016692:Receptors, Antigen, T-Cell, gamma-delta