High frequency of clonal immunoglobulin or T cell receptor gene rearrangements in acute myelogenous leukemia expressing terminal deoxyribonucleotidyltransferase.
Ig and T cell receptor rearrangements have been used as irreversible markers of lineage and clonality in the study of B- and T-lymphoid populations. We have addressed the issue of lymphoid lineage specificity of these rearrangements by analyzing a panel of 25 TdT- acute myelogenous leukemias, 13 TdT+ AMLs, and 4 TdT+ undifferentiated leukemias. We report that while gene rearrangements represent extremely rare events in classical TdT- AML (less than 8%), rearrangements of either the Ig or T beta locus or both were detectable in the majority of the TdT+ AMLs (greater than 60%), and rearrangements of both loci were detectable in all of the TdT+ undifferentiated leukemias. These data demonstrate a significant association between TdT expression and Ig or T beta gene rearrangements even outside the lymphoid lineage, further supporting a role for TdT in Ig and T cell receptor gene assembly. These data also indicate that a coordinated program of lymphoid gene expression involving TdT-CD7-expression and Ig/T beta rearrangements can be activated before myeloid commitment. Whether the activation of this program represents a normal, albeit rare, event in early myelopoiesis or a transformation-related event present only in leukemic cells remains to be determined.
Seremetis
S V
SV
Pelicci
P G
PG
Tabilio
A
A
Ubriaco
A
A
Grignani
F
F
Cuttner
J
J
Winchester
R J
RJ
Knowles
D M
DM
Dalla-Favera
R
R
D002454:Cell Differentiation; D004253:DNA Nucleotidylexotransferase / Q000032:analysis*; D004254:DNA Nucleotidyltransferases / Q000032:analysis*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D007938:Leukemia / Q000145:classification / Q000175:diagnosis; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D008223:Lymphoma / Q000145:classification / Q000175:diagnosis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011995:Recombination, Genetic
D007136:Immunoglobulins; D011948:Receptors, Antigen, T-Cell; D004254:DNA Nucleotidyltransferases; D004253:DNA Nucleotidylexotransferase