L. Trumper et al., NPM ALK FUSION MESSENGER-RNA EXPRESSION IN HODGKIN AND REED-STERNBERGCELLS IS RARE BUT DOES OCCUR - RESULTS FROM SINGLE-CELL CDNA ANALYSIS/, Annals of oncology, 8, 1997, pp. 83-87
Background: The translocation t(2;5)(p23;q35) leads to the fusion of t
he nucleophosmin gene (NPM) on chromosome 5q35 to the recently describ
ed receptor kinase ALK on 2p23. It is characteristic of a subgroup of
CD30+ large-cell anaplastic non-Hodgkin's lymphoma (ALCL). Since some
cases of Hodgkin's disease (HD) and ALCL share common features, a comm
on pathogenesis has been proposed in a report of the expression of NPM
/ALK fusion mRNA in 11/13 Hodgkin's lymphomas. Patients and methods: W
e approached this question by micro-manipulatory isolation of single H
odgkin and Reed-Sternberg (H-RS) cells and subsequent RT-PCR amplifica
tion of NPM/ALK fusion cDNA from these single cells. Results: Specific
ity of cell selection was shown by the HD-specific pattern of EBV-gene
expression in single H-RS cells. In 4 out of 7 cases, NPM/ALK fusion
cDNA was detected in the RNA. from whole lymph node tissue. In 2 out o
f 9 cases, NPM/ALK fusion sequences were amplified from single H-RS ce
lls, albeit in a very low frequency (< 5%): Conclusions: These data in
dicate that NPM/ALK fusion transcripts do not play an early role in th
e pathogenesis of HD. Whether the rare expression of NPM/ALK is the re
sult of clonal heterogeneity or an indication for clonal evolution and
progression toward ALCL can only be answered by the repeated analysis
of indicator cases during the course of the disease.