Incidence of lineage promiscuity in acute myeloblastic leukemia: diagnostic implications of immunoglobulin and T-cell receptor gene rearrangement analysis and immunological phenotyping.
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.
Oster
W
W
Department of Hematology, Johannes Gutenberg-Universität, Mainz, Federal Republic of Germany.
König
K
K
Ludwig
W D
WD
Ganser
A
A
Lindemann
A
A
Mertelsmann
R
R
Herrmann
F
F
D000328:Adult; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation; D002648:Child; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics* / Q000473:pathology; D010641:Phenotype
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains