The cell origin of the rare terminal deoxynucleotidyl transferase (TdT)-positive acute myeloid leukemias (AML) was investigated at the molecular level, by examining the configuration of the Ig H (Igh) and L (Ig kappa, Ig lambda) chain gene regions, and of the T cell receptor (TCR) beta and T cell rearranging (TRG) gamma loci. In 8 of the 10 TdT+ AML analyzed (classified as myeloid according to morphological and cytochemical criteria, and to the reactivity with one or more antimyeloid mAbs), a rearrangement of the Igh chain gene was found. In TdT- AML, evidence of an Igh gene reorganization was instead observed only in 2 of the 42 patients studied. Furthermore, evidence of TCR-beta and/or TRG-gamma gene rearrangement was observed in four AML, all of which belonged to the Igh-rearranged TdT+ group. In three cases (one TdT+ and two TdT-), the Ig kappa L chain gene was also in a rearranged position. These findings demonstrate a highly significant correlation between TdT expression and DNA rearrangements at the Igh and TCR chain gene regions and support the view that this enzyme plays an important role in the V-(D)-J recombination machinery. Overall, the genomic configuration, i.e., JH gene rearrangement sometimes coupled to a kappa L chain and TCR gene reorganization, similar to that found in non-T-ALL, suggests that in most cases of TdT+ AML, the neoplastic clone, despite the expression of myeloid-related features, is characterized by cells molecularly committed along the B cell lineage.
Rearrangements of immunoglobulin and T cell receptor beta and gamma genes are associated with terminal deoxynucleotidyl transferase expression in acute myeloid leukemia.
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R Foa, G Casorati, M C Giubellino, G Basso, R Schirò, G Pizzolo, F Lauria, M P Lefranc, T H Rabbitts, N Migone; Rearrangements of immunoglobulin and T cell receptor beta and gamma genes are associated with terminal deoxynucleotidyl transferase expression in acute myeloid leukemia.. J Exp Med 1 March 1987; 165 (3): 879–890. doi: https://doi.org/10.1084/jem.165.3.879
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