Variable numbers of BCR-ABL transcripts persist in CML patients who achieve complete cytogenetic remission with interferon-alpha.
A substantial minority of patients with chronic myeloid leukaemia (CML) achieve a complete response to treatment with interferon-alpha (IFN-alpha), defined as the disappearance of Philadelphia chromosome positive metaphases or, for patients who are Philadelphia chromosome negative but BCR-ABL positive, the disappearance of the leukaemic clone as assayed by Southern blot. We have measured the levels of BCR-ABL transcripts in 20 such patients by quantitative PCR. Results were standardized for both quality and quantity of cDNA by quantification of ABL as an internal control. All 20 patients had evidence of residual disease; the median number of transcripts was 750/micrograms RNA (range 10-22,000) and the median BCR-ABL/ABL ratio was 0.17% (range 0.0008-3.6%). Our findings show that CML has not been eradicated in any patient and that the quantity of residual disease in complete responders may vary by as much as four orders of magnitude.
Hochhaus
A
A
LRF Centre for Adult Leukaemia, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Lin
F
F
Reiter
A
A
Skladny
H
H
van Rhee
F
F
Shepherd
P C
PC
Allan
N C
NC
Hehlmann
R
R
Goldman
J M
JM
Cross
N C
NC
D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012074:Remission Induction; D014158:Transcription, Genetic
D016898:Interferon-alpha; D016044:Fusion Proteins, bcr-abl