DESIGN AND VALIDATION OF DNA-PROBE SETS FOR A COMPREHENSIVE INTERPHASE CYTOGENETIC ANALYSIS OF ACUTE MYELOID-LEUKEMIA

The objective of this study was to design DNA probe sets that enable t he detection of chromosome aberrations in acute myeloid leukemia (AML) by interphase cytogenetics using fluorescence in situ hybridization ( FISH) and to compare the results of interphase cytogenetics with those of conventional chromosome banding analysis. One hundred five consecu tive patients with adult AML entered on a multicenter treatment trial were studied with a comprehensive set of DNA probes recognizing the mo st relevant AML-associated structural and numerical chromosome aberrat ions: translocations t(8;21), t(15;17), and t(11q23); inversion inv(16 ); chromosomal deletions (5q-, 7q-, 9q-, 12p-, 13q-, 17p-, and 20q-); and chromosomal aneuploidies. Interphase cytogenetics was particularly sensitive for detecting the AML-specific gene fusions: 3 additional c ases of inv(ls) and 1 additional case of t(8;21) were identified by FI SH that were missed by banding analysis, whereas equal numbers ok t(11 q23) and t(15;17) were detected. Five additional cases of trisomy 8q, 3 more cases of trisomy 11q, and 2 more cases of trisomies 21q and 22q were shown by FISH. These aberrations were either masked in complex k aryotypes or identified in cases in which conventional banding analysi s failed. On the other hand, the DNA probes selected were not informat ive to defect 1 case of 5q-, 9q-, and 20q-. In 5 cases, clonal aberrat ions were defected on banding analysis for which no FISH probes were s elected. In conclusion, interphase cytogenetics proved to be more sens itive for detecting AML-specific chimeric gene fusions and some partia l trisomies. Interphase cytogenetics provides a powerful technique com plementary and, with further development of diagnostic DNA probes, eve n an alternative to chromosome banding studies for the cytogenetic ana lysis of AML. (C) 1996 by The American Society of Hematology.