Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: A cancer and leukemia group B study

K. Mrózek, T. W. Prior, C. Edwards, G. Marcucci, A. J. Carroll, P. J. Snyder, P. R K Koduru, K. S. Theil, M. J. Pettenati, K. J. Archer, M. A. Caligiuri, J. W. Vardiman, J. E. Kolitz, R. A. Larson, C. D. Bloomfield

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Abstract

Purpose: To prospectively compare cytogenetics and reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22), aberrations characteristic of core-binding factor (CBF) acute myeloid leukemia (AML), in 284 adults newly diagnosed with primary AML. Patients and Methods: Cytogenetic analyses were performed at local laboratories, with results reviewed centrally. RT-PCR for AML 1/ETO and CBFβ/MYH11 was performed centrally. Results: CBF AML was ultimately identified in 48 patients: 21 had t(8;21) or its variant and AML1/ETO, and 27 had inv(16)/t(16;16), CBFβ/MYH11, or both. Initial cytogenetic and RT-PCR analyses correctly classified 95.7% and 96.1% of patients, respectively (P = .83). Initial cytogenetic results were considered to be false-negative in three AML1/ETO-positive patients with unique variants of t(8;21), and in three CBFβ/ MYH11/-positive patients with, respectively, an isolated +22; del(16)(q22),+22; and a normal karyotype. The latter three patients were later confirmed to have inv(16)/t(16;16) cytogenetically. Only one of 124 patients reported initially as cytogenetically normal was ultimately RT-PCR-positive. There was no false-positive cytogenetic result. Initial RT-PCR was falsely negative in two patients with inv(16) and falsely positive for AML1/ETO in two and for CBFβ/MYH11 in another two patients. Two patients with del(16)(q22) were found to be CBFβ/MYH11-negative. M4Eo marrow morphology was a good predictor of the presence of inv(16)/t(16;16). Conclusion: Patients with t(8;21) or inv(16) can be successfully identified in prospective multi-institutional clinical trials. Both cytogenetics and RT-PCR detect most such patients, although each method has limitations. RT-PCR is required when the cytogenetic study fails; it is also required to determine whether patients with suspected variants of t(8;21), del(16)(q22), or +22 represent CBF AML. RT-PCR should not replace cytogenetics and should not be used as the only diagnostic test for detection of CBF AML because of the possibility of obtaining false-positive or false-negative results.

Original languageEnglish (US)
Pages (from-to)2482-2492
Number of pages11
JournalJournal of Clinical Oncology
Volume19
Issue number9
DOIs
StatePublished - May 1 2001

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mrózek, K., Prior, T. W., Edwards, C., Marcucci, G., Carroll, A. J., Snyder, P. J., Koduru, P. R. K., Theil, K. S., Pettenati, M. J., Archer, K. J., Caligiuri, M. A., Vardiman, J. W., Kolitz, J. E., Larson, R. A., & Bloomfield, C. D. (2001). Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: A cancer and leukemia group B study. Journal of Clinical Oncology, 19(9), 2482-2492. https://doi.org/10.1200/JCO.2001.19.9.2482