Monitoring of chronic myelogenous leukemia patients by semiquantitive bcr-abl protein detection in peripheral blood mononuclear cells

M. Schleunine, J. Mittermuller, H. J. Kolb

Research output: Contribution to journalArticlepeer-review


Nearly all cases of chronic myelogenous leukemia (CML) carry an abnormal chromosome 22, the specific Philadelphia chromosome (Ph). The Ph is characterized by a fusion of the second exon of the abl gene (a2) from chromosome 9 into the central portion of the bcr gene, Most frequently a2 is fused to one of 2 small exons in the major breakpoint cluster region of the bcr gene, termed b2 and b3, Following transcription and alternative splicing both gene fusions generate mRNA encoding for a bcr-abl protein of more than 2000 amino acids (p210). Monitoring of CML patients undergoing therapy is usually done by chromosomal analysis of bone marrow. To allow more fcquent follow-ups we have assessed the value of p2 10 protein detection in peripheral blood mononuclear cells. Quantification was achieved by comparing the relative intensities of the p210 bands with those of the normal abl protein (p!45) Serial dilution of Ph positive K562 cells with Ph negative HL60 or KG! cells revealed a linear correlation between the p2IO/p!45 ratio and the number of Ph positive cells (r=0.998; p<0.001) with a sensitivity of detecting less than 1% Ph positive cells in 5xl06 cells. Ninety-six consecutive patients were enrolled in the study and a total of 155 Western blot analyses have been performed and compared to same day chromosomal analyses of bone marrow. Parallel RT-PCR analyses have been done on 99 occasions. All patients with positive cvtogeneric findings proved to be positive for p210. In 23 instances p210 was detectable despite negative chromosomal analysis. In 16 samples these results were confirmed by RT-PCR. In patients with partial cytogenetic remission (n=26) the results of the p210 assay correlated significantly with the percentage of Ph positive metaphases (r=0.69; p<0.001). In conclusion, monitoring of CML patients by quantification of the bcrabl protein is a feasible and sensitive alternative to chromosomal analysis of bone marrow.

Original languageEnglish
Pages (from-to)794
Number of pages1
JournalExperimental Hematology
Issue number8
StatePublished - 1998
Externally publishedYes


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