TY - JOUR
T1 - Detection of two alternative bcr/abl mRNA junctions and minimal residual disease in Philadelphia chromosome positive chronic myelogenous leukemia by polymerase chain reaction
AU - Lee, M. S.
AU - LeMaistre, A.
AU - Kantarjian, H. M.
AU - Talpaz, M.
AU - Freireich, E. J.
AU - Trujillo, J. M.
AU - Stass, S. A.
PY - 1989
Y1 - 1989
N2 - 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 (rα-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.
AB - 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 (rα-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.
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U2 - 10.1182/blood.v73.8.2165.bloodjournal7382165
DO - 10.1182/blood.v73.8.2165.bloodjournal7382165
M3 - Article
C2 - 2730954
AN - SCOPUS:0024406150
SN - 0006-4971
VL - 73
SP - 2165
EP - 2170
JO - Blood
JF - Blood
IS - 8
ER -