A comparative analysis of cytoplasmic Mu (Cμ) expression in acute lymphoblastic leukemia by molecular and immunologic techniques: Identification of leukemia cases expressing Cμ mRNA transcripts in the absence of detectable Cμ proteins

Among acute lymphoblastic leukemias derived from the B-cell lineage, the subset of cases expressing cytoplasmic μ heavy chain proteins (Cμ) in the absence of surface immunoglobulin has been designated pre-B-cell acute lymphoblastic leukemia. This group, traditionally identified using immunologic smear techniques, has been associated with a poor prognosis in some series. In a comparative study, 25 cases of B-lineage acute lymphoblastic leukemia were analyzed for Cμ expression using molecular and immunologic techniques. RNA derived from cryopreserved blast cells was hybridized in both Northern and slot-blot analyses using a probe (pBZ311) containing four exons of the human immunoglobulin heavy chain μ constant region gene. Expression of Cμ proteins was assessed simultaneously by slide immunofluorescence and flow cytometric techniques in all samples. These studies were correlated with immunoglobulin heavy and light chain gene rearrangements, cell-surface immunophenotype, cytogenetics, and other clinicopathologic features. Cμ mRNA transcripts were detected in 14 of 25 cases, whereas Cμ proteins were detected in only 9 of these cases using flow cytometric techniques. Only four of these nine cases were positive by slide immunofluorescence techniques. These studies imply that molecular and flow cytometric techniques may be a more sensitive means to assess Cμ expression. The identification of five cases that expressed Cμ mRNA transcripts in the absence of detectable Cμ proteins also suggests that molecular techniques may be valuable in identifying a unique subgroup of pre-B-cell acute lymphoblastic leukemia cases that contain Cμ mRNA transcripts, but lack Cμ proteins.