Quantitative acute leukemia cytogenetics

Abstract

Using literature data on cytogenetic abnormalities in 3,612 cases of acute myeloid leukemia (AML) and 1,551 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 I. 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 LI. The highest (1.0) positive predictive values in the AML versus ALL comparison were found for t(1;3)(p36;q21), inv(3)(q21q26), 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;q11), dup(1)(q12–21q31–32), 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.