Molecular analysis of acute undifferentiated leukemia: Two distinct subgroups at the DNA and RNA levels

Abstract

On the basis of negativity for myeloperoxidase (MPO) and absence of lineage-associated antigens on the cell surface, 11 children were diagnosed as having acute undifferentiated leukemia. To analyze the molecular events associated with hematopoietic cell differentiation, we analyzed the configuration of the immunoglobulin (Ig) and T-cell receptor (TCR) δ, α, γ, and β genes in these patients. In parallel, transcription of the genes for MPO, terminal deoxynucleotidyltransferase (TdT), CD3-γ, Ig-μ, TCR-γ, and β was also examined. Six patients showed rearrangements of both the Ig heavy (H) and TCR-δ genes, frequently accompanied with Ig-κ, TCR-α, γ, and β gene rearrangements. These findings indicated that the leukemic cells from the six patients had been committed to the lymphoid lineage. This concept was supported by the presence of TdT transcripts in three analyzed specimens from these patients. In contrast, the remaining five patients did not display rearrangements of the Ig or TCR genes, and TdT transcripts were undetectable in two patients tested. MPO transcripts were not detected in four patients analyzed, thus providing no evidence of myeloid differentiation. After hybridization with the CD3-γ gene, three of six patients showed transcripts, one patient with rearrangements of the Ig-H, TCR-δ, α, γ, and β genes also had full-length TCR-β and γ transcripts, indicating a T-precursor-cell origin of the leukemic cells from this patient. The Ig and TCR genes were in the germline configuration in the other two patients with CD3-γ transcripts. One of them did not express the CD7 antigen but did express the CD33 antigen on the cell surface, suggesting that CD3-γ transcription may not always be an event restricted to cells differentiating along the T-cell lineage.