Plasma RNA as an alternative to cells for monitoring molecular response in patients with chronic myeloid leukemia.
OBJECTIVE
Quantitation of BCR-ABL mRNA is emerging as the standard of care to monitor the status of chronic myeloid leukemia (CML). Peripheral blood plasma was analyzed in this study because of previous detection of nucleic acids and proteins from tumor cells in plasma samples.


METHODS
Reverse transcriptase polyemrase chain reaction was used to establish ratios of BCR-ABL:ABL mRNA in peripheral blood cells and plasma, and absolute levels of BCR-ABL mRNA per unit volume of plasma. Samples from 160 CML patients and 180 control individuals without CML were tested. Cells and plasma samples from 93 of the CML patients were re-analyzed 3-12 months after imatinib treatment.


RESULTS
Ratios of BCR-ABL:ABL mRNA in paired cell and plasma samples of the 160 CML patients correlated significantly (r=0.83; p<0.001). When results were compared directly using the sign test, the pre-therapy plasma results were significantly different from those from peripheral blood cells (p=0.028), but not bone marrow cells (p=0.119). Absolute levels of BCR-ABL mRNA in plasma strongly correlated with many laboratory characteristics in pre-therapy CML patients. Higher BCR-ABL: ABL ratios were detected in plasma samples at all time points after treatment, although this was significant only at 3 months (p=0.0003). In cases in which results from the assays disagreed, minimal residual disease was detected in plasma samples significantly more frequently than in cell samples (p<0.001).


CONCLUSIONS
Plasma was a reliable source for monitoring BCR-ABL mRNA levels. Minimal residual disease detection from plasma was more sensitive than from cell samples. Our results suggest that absolute levels of BCR-ABL mRNA per unit volume of plasma may reflect tumor load.
Ma
Wanlong
W
Quest Diagnostics Nichols Institute 33608 Ortega Highway, Rm#108B, San Juan Capistrano, CA 92690-6130, USA.
Tseng
Richard
R
Gorre
Mercedes
M
Jilani
Iman
I
Keating
Michael
M
Kantarjian
Hagop
H
Cortes
Jorge
J
O'Brien
Susan
S
Giles
Francis
F
Albitar
Maher
M
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D016022:Case-Control Studies; D017931:DNA Primers / Q000737:chemistry; D016044:Fusion Proteins, bcr-abl / Q000097:blood / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000235:genetics / Q000628:therapy*; D008991:Monitoring, Physiologic / Q000379:methods*; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D012313:RNA / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D001549:Benzamides; D017931:DNA Primers; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012313:RNA; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl