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  • Title: Incidence of lineage promiscuity in acute myeloblastic leukemia: diagnostic implications of immunoglobulin and T-cell receptor gene rearrangement analysis and immunological phenotyping.
    Author: Oster W, König K, Ludwig WD, Ganser A, Lindemann A, Mertelsmann R, Herrmann F.
    Journal: Leuk Res; 1988; 12(11-12):887-95. PubMed ID: 2851073.
    Abstract:
    Sixty-nine blood or bone marrow samples from both children and adults with acute myeloblastic leukemia (AML) were investigated to elucidate the frequency of immunoglobulin (IG) and T-cell receptor (TCR)-gene rearrangements. Non-germline configuration for the IG heavy chain (h) gene was detected in the specimens of nine patients of various subtypes according to the French-American-British classification (FAB), including FAB M1, M2, M4 and M5. Rearrangement of the IG kappa chain (k) gene was present in one of these cases which simultaneously revealed a rearranged TCR-beta (b) chain gene. In another two AML samples we found TCR-b gene rearrangements, in one case in combination with an IG-h gene rearrangement. IG-h gene rearrangements were detected in 10 cases, in one case in conjunction with an IG-kappa (k) and TCR-b gene rearrangement. A highly significant correlation between the occurrence of DNA rearrangements of the IG-h locus and nuclear staining with the enzyme terminal deoxynucleotidyl transferase (TdT) and surface expression of the CD 19 and CD 34 antigen could be identified: all 10 TdT positive AML samples rearranged IG-h. Similarly, six out of 69 AML samples exhibited surface expression of CD 19, five of these in combination with CD 34 and all of them rearranged the IG-h gene. The one leukemia with TCR-b gene rearrangement only was TdT positive as well, but did not express CD 19 or CD 34. We conclude that IG-h gene is rearranged in a substantial proportion of AML, strongly associated with a specific immunophenotype (TdT+, CD19+, CD34+), whereas TCR-b gene rearrangement appears more rarely. No positive correlation between occurrence of IG-h and TCR-b gene-rearrangements and one AML FAB-subtype was found, although a clustering of M1 and M4 FAB subtypes in the AML group showing reconstructed IG-h gene became evident.
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