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Quantification of Residual Disease in Chronic Myelogenous Leukemia Patients on Interferon-α Therapy by Competitive Polymerase Chain Reaction

Interferon-α (IFN-α) induces cytogenetic responses of variable degree in patients with chronic myelogenous leukemia (CML). We sought to establish the relationship between BCR-ABL transcript numbers measured by competitive 2-step reverse transcription polymerase chain reaction (RT-PCR) and cytogeneti...

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Published in:Blood 1996-02, Vol.87 (4), p.1549-1555
Main Authors: Hochhaus, Andreas, Lin, Feng, Reiter, Andreas, Skladny, Heyko, Mason, Philip J., Rhee, Frits van, Shepherd, Patricia C.A., Allan, Norman C., Hehlmann, Rudiger, Goldman, John M., Cross, Nicholas C.P.
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container_end_page 1555
container_issue 4
container_start_page 1549
container_title Blood
container_volume 87
creator Hochhaus, Andreas
Lin, Feng
Reiter, Andreas
Skladny, Heyko
Mason, Philip J.
Rhee, Frits van
Shepherd, Patricia C.A.
Allan, Norman C.
Hehlmann, Rudiger
Goldman, John M.
Cross, Nicholas C.P.
description Interferon-α (IFN-α) induces cytogenetic responses of variable degree in patients with chronic myelogenous leukemia (CML). We sought to establish the relationship between BCR-ABL transcript numbers measured by competitive 2-step reverse transcription polymerase chain reaction (RT-PCR) and cytogenetic status in CML patients treated with IFN-α. A total of 250 peripheral blood and 55 bone marrow samples from 127 Philadelphia chromosome positive (Ph+) and 6 Ph-/BCR-ABL+ CML patients were investigated. Twenty-one patients were studied at diagnosis and 112 on treatment. Of the 106 Ph+ patients treated with IFN-α, 24 had a complete cytogenetic response, 21 a partial response, 12 a minor response, 26 no response, and 23 were unknown. Using nested RT-PCR, all 305 samples were positive for BCR-ABL transcripts. To standardize results for variability in RNA and cDNA quantity and quality, we quantified total ABL transcripts in each sample as internal control. The validity of ABL as internal control was shown by comparison with glucose-6-phosphate dehydrogenase transcript levels in 145 samples. The median BCR-ABL transcript numbers (and BCR-ABL/ABL ratios expressed as percentages) were 400/ μg RNA (0.04%) in complete responders, 20,500/μg RNA (7.1%) in partial responders, 170,000/μg RNA (21.0%) in minor responders, and 430,000/μg RNA (58.7%) in nonresponders (P < .001). The cytogenetic results correlated with the BCR-ABL transcript numbers (r = .82; P < .001) and BCR-ABL/ABL ratios (r = .84; P < .001). Grouping the ratios BCR-ABL/ABL as less than 2%, 2% to 14%, and greater than 14% to compare with cytogenetic complete response, partial response, and minor/nonresponse, the concordance between the two methods was 82% (χ2P < .0001). We conclude that quantitative PCR with internal controls is a sensitive and reliable method for monitoring patients on IFN-α and reduces the need for repeated marrow investigations.
doi_str_mv 10.1182/blood.V87.4.1549.bloodjournal8741549
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We sought to establish the relationship between BCR-ABL transcript numbers measured by competitive 2-step reverse transcription polymerase chain reaction (RT-PCR) and cytogenetic status in CML patients treated with IFN-α. A total of 250 peripheral blood and 55 bone marrow samples from 127 Philadelphia chromosome positive (Ph+) and 6 Ph-/BCR-ABL+ CML patients were investigated. Twenty-one patients were studied at diagnosis and 112 on treatment. Of the 106 Ph+ patients treated with IFN-α, 24 had a complete cytogenetic response, 21 a partial response, 12 a minor response, 26 no response, and 23 were unknown. Using nested RT-PCR, all 305 samples were positive for BCR-ABL transcripts. To standardize results for variability in RNA and cDNA quantity and quality, we quantified total ABL transcripts in each sample as internal control. The validity of ABL as internal control was shown by comparison with glucose-6-phosphate dehydrogenase transcript levels in 145 samples. The median BCR-ABL transcript numbers (and BCR-ABL/ABL ratios expressed as percentages) were 400/ μg RNA (0.04%) in complete responders, 20,500/μg RNA (7.1%) in partial responders, 170,000/μg RNA (21.0%) in minor responders, and 430,000/μg RNA (58.7%) in nonresponders (P &lt; .001). The cytogenetic results correlated with the BCR-ABL transcript numbers (r = .82; P &lt; .001) and BCR-ABL/ABL ratios (r = .84; P &lt; .001). Grouping the ratios BCR-ABL/ABL as less than 2%, 2% to 14%, and greater than 14% to compare with cytogenetic complete response, partial response, and minor/nonresponse, the concordance between the two methods was 82% (χ2P &lt; .0001). 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We sought to establish the relationship between BCR-ABL transcript numbers measured by competitive 2-step reverse transcription polymerase chain reaction (RT-PCR) and cytogenetic status in CML patients treated with IFN-α. A total of 250 peripheral blood and 55 bone marrow samples from 127 Philadelphia chromosome positive (Ph+) and 6 Ph-/BCR-ABL+ CML patients were investigated. Twenty-one patients were studied at diagnosis and 112 on treatment. Of the 106 Ph+ patients treated with IFN-α, 24 had a complete cytogenetic response, 21 a partial response, 12 a minor response, 26 no response, and 23 were unknown. Using nested RT-PCR, all 305 samples were positive for BCR-ABL transcripts. To standardize results for variability in RNA and cDNA quantity and quality, we quantified total ABL transcripts in each sample as internal control. The validity of ABL as internal control was shown by comparison with glucose-6-phosphate dehydrogenase transcript levels in 145 samples. The median BCR-ABL transcript numbers (and BCR-ABL/ABL ratios expressed as percentages) were 400/ μg RNA (0.04%) in complete responders, 20,500/μg RNA (7.1%) in partial responders, 170,000/μg RNA (21.0%) in minor responders, and 430,000/μg RNA (58.7%) in nonresponders (P &lt; .001). The cytogenetic results correlated with the BCR-ABL transcript numbers (r = .82; P &lt; .001) and BCR-ABL/ABL ratios (r = .84; P &lt; .001). Grouping the ratios BCR-ABL/ABL as less than 2%, 2% to 14%, and greater than 14% to compare with cytogenetic complete response, partial response, and minor/nonresponse, the concordance between the two methods was 82% (χ2P &lt; .0001). We conclude that quantitative PCR with internal controls is a sensitive and reliable method for monitoring patients on IFN-α and reduces the need for repeated marrow investigations.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>8608246</pmid><doi>10.1182/blood.V87.4.1549.bloodjournal8741549</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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ispartof Blood, 1996-02, Vol.87 (4), p.1549-1555
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source ScienceDirect Journals
subjects Adolescent
Adult
Aged
Base Sequence
Child
DNA Primers - chemistry
Female
Fusion Proteins, bcr-abl - genetics
Humans
Interferon-alpha - therapeutic use
Karyotyping
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis
Male
Middle Aged
Molecular Sequence Data
Neoplasm, Residual - diagnosis
Polymerase Chain Reaction - methods
RNA, Neoplasm - genetics
title Quantification of Residual Disease in Chronic Myelogenous Leukemia Patients on Interferon-α Therapy by Competitive Polymerase Chain Reaction
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