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Detection of two alternative bcr/abl mRNA junctions and minimal residual
disease in Philadelphia chromosome positive chronic myelogenous leukemia by
polymerase chain reaction
MS Lee, A LeMaistre, HM Kantarjian, M Talpaz, EJ Freireich, JM Trujillo and SA Stass
Department of Hematology, University of Texas, M.D. Anderson Cancer Center,
Houston 77030.
The Philadelphia (Ph') chromosome in chronic myelogenous leukemia (CML)
results in fusion of the bcr gene and c-abl oncogene, which transcribes
into two types of chimeric bcr/abl mRNAs: the L-6 junction and the K-28
junction. By means of a highly sensitive assay, combination of reverse
transcription and polymerase chain reaction (RT/PCR), we analyzed 38 blood
samples obtained from 31 patients with Ph'-positive CML and two patients
with Ph'-negative bcr rearranged CML. Among the 21 samples obtained in
chronic phase, eight patients had the L-6 mRNA, 11 had the K-28 mRNA, and
two had both the L-6 and K-28 mRNAs. Among the nine samples obtained in
blast crisis, four contained the L-6 mRNA, two contained the K-28 mRNA, and
three contained both the K-28 and L-6 mRNAs. This finding supports the
concept of alternative splicing of bcr/abl mRNAs transcribed in
Ph'-positive CML. However, it appears to be a rare event. Of the eight
samples obtained from eight patients who had achieved complete cytogenetic
remission and negativity for bcr region rearrangement for 6 months to 3
years after recombinant alpha interferon (r alpha-IFN) therapy, all of them
showed evidence of minimal residual Ph'-positive clones as detected by the
RT/PCR assay. This finding suggests that interferon therapy suppresses the
proliferation of the Ph'-positive clones, but it does not completely
eradicate the Ph'-positive stem cells.
Volume 73,
Issue 8,
pp. 2165-2170,
06/01/1989
Copyright © 1989 by The American Society of Hematology
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