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

Purpose: To prospectively compare cytogenetics and reverse transcriptase-po lymerase 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 f actor (CBF) acute myeloid leukemia (AML), in 284 adults newly diagnosed wit h primary AML. Patients and Methods: Cytogenetic analyses were performed at local laborato ries, with results reviewed centrally. RT-PCR for AML1/ETO and CBF beta /MY H11 was performed centrally. Results: CBF AML was ultimately identified in 48 patients: 21 had t(8;21) o r its variant and AML1/ETO, and 27 had inv(16)/t(16;16), CBF beta /MYH11, o r 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 wi th unique variants of t(8;21), and in three CBF beta/ MYH11-positive patien ts with, respectively, an isolated +22; del(16)(q22),+22; and a normal kary otype. The latter three patients were later confirmed to have inv(16)/t(16; 16) cytogenetically. Only one of 124 patients reported initially as cytogen etically normal was ultimately RT-PCR-positive. There was no false-positive cytogenetic result. initial RT-PCR was falsely negative in two patients wi th inv(16) and falsely positive for AML1/ETO in two and far CBF beta /MYH11 in another two patients. Two patients with del(16)(q22) were found to be C BF beta /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 de termine 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 o f the possibility of obtaining false-positive or false-negative results. J Clin Oncol 19:2482-2492. (C) 2001 by American Society of Clinical Oncology.