QUANTITATIVE ACUTE-LEUKEMIA CYTOGENETICS

Using literature data on cytogenetic abnormalities in 3,612 cases of acute myeloid leukemia (AML) and 1,55 1 cases of acute lymphocytic leukemia (ALL), we have attempted to quantify the information value of finding the typical ALL- and AML-associated chromosome aberrations. Sensitivity, specificity, and predictive value of finding or not finding a given aberration were calculated for several diagnostic scenarios: for the differential diagnosis between ALL and AML when the patient is known to have acute leukemia, for the differential diagnosis among AML FAB subtypes in a patient with known AML, and for the differential diagnosis between ALL FAB subtypes in a patient with known ALL The specificities were generally high, close to 1. The highest sensitivities in AML were found for + 8, t(15;17)(q22;q11), t(8;21)(q22;q22), and - 7 (all > 0. 1), and in ALL for t(9;22)(q34;q11), t(4;11)(q21;q23), and + 21 (again all > 0.1). In the AML subtypes, the highest sensitivities were 0.89 for t(15;17)(q22;q11) in M3, followed by 0.40 for t(8;21)(q22;q22) in M2, 0.30 for inv(16)(p13q22)/del(16)(q22)/t(16;16)(p13;q22) in M4, and 0.16 for t(9;11)(p21;q23) in M5. in the ALL subtypes, the highest sensitivities were 0.71 and 0. 11 for t(8;14)(q24;q32) and t(8;22)(q24;q11), respectively, in L3, 0.23 for t(9;22)(q34;q11) in L2, and 0. 18 and 0. 13 for +21 and t(4;11)(q21;q23), respectively, in L1. The highest (1.0) positive predictive values in the AML versus ALL comparison were found for t(1;3)(p36;q21),inv(3)(q2lq26),t(6;9)(p23;q34),t(7;11)(p15;p15),t(8;16)(p11;p13),t(8;21)(q22;q22),t(15;17)(q22;q11),and,as sole anomalies, for +4, +9, and +11. in the reverse comparison, ALL versus AML, positive predictive values of 1.0 were found for t(1;14)(p32-34;q1l), dup(1)(q12-2lq3l-32), t(2;8)(p12;q24), t(8;14)(q24;q32), t/dic(9;12)(p11-12;p11-13), t(10;14)(q24;q11),and t(11;14)(p13;q11).Among the AML subgroups, the highest predictive values were: 1.0 for M3 if t(15;17), 0.91 for M2 if t(8;21), 0.86 for M4 if inv/del(16)/t(16;16),and 0.82 for M5 if t(9;11). Among the ALL subtypes, positive predictive values of > 0.8 were reached only for the L3-associated aberrations t(2;8) (1.0), t(8; 14) (0.95), t(8;22) (0.87), and dup(1) (0.80). The highest negative predictive values were in AML 0.98 that the disease is not M3 if t(15;17) is not found, and in ALL 0.96 that the patient does not have L3 if a t(8;14) is not detected.