The Relationship between the Immunophenotypic Profile and Cytogenetic Abnormalities in Acute Myeloid Leukemia.

Abstract

We studied the immunophenotypic characteristics of 459 consecutive adult AML patients and their correlation with karyotype. Immunophenotype was performed using a panel of 26 directly conjugated monoclonal antibodies. Cytogenetic analysis was performed using a standard G-banding technique. Karyotype was available in 394 patients (not done in 15, failed in 50): 1) 45 (11.4%) were t(15;17) APL patients with a mature myeloid phenotype (HLA-DR-/CD13+ and/or CD33+). CD2 and CD56 were expressed in 20% and 13.3% of cases, respectively. CD11b-positivity was less frequent than in the other cytogenetic groups. The markers significantly associated with t(15;17) were: presence of CD2 (two tailed Fisher exact test: p=.003) and CD117 (p=.01), absence of CD4dim (p<.001), CD7 (p<.001), CD11b (p<.001), CD11c (p<.001), CD14 (p<.001), CD34 (p<.001), TdT (p=.03) and HLA-DR (p<.001). 2) 12 (3%) showed t(8;21) and were characterized by CD34+/CD19+/CD13+<CD33+ in more than 80% of blasts. CD56 were expressed in 87.5%. CD11b was positive only in 8.3% and CD14 was constantly negative. In univariate analysis, t(8;21) was associated with CD11b- (p=.03), CD19+ (p<.001) and CD56+(p<.001). 3) 23 (5.8%) had inv(16) or t(16;16) with CD13+/CD33+ in >90% of blasts, CD34+ in 70%, MPO+ in 95.8% and HLA-DR+ in 89.3%. The association with CD14 and TdT was of borderline statistical significance. 4) 24 (6.1%) had −5/5q- with more than 80% of blasts CD117+/CD13+>CD33+. CD34 was positive in 62.9% of cases, CD7 in 33%, CD11b in 35.7%, CD11c in 67.8% and CD14 in 7.1%. CD15-positivity was less frequent than in other AML subtypes. Univariate analysis showed a trend of positive association with CD7 and CD117. 5) 40 (10.2%) showed −7/7q-, with CD13+>CD33+ detected in more than 80%, CD7 in 33.3%, CD11b in 72.7%, CD15 in 55%, CD34 in 73.3%. Abnormal CD16/CD33 and/or CD11b/CD66b myeloid cell pattern was detected in 40% of cases (p=.001). −7/7q- were significantly associated with CD34 (p=.02) and CD7 (p=.04). 6) 41 (10.4%), had complex karyotype (≥3 abn) with a similar antigenic profile than group 4) and 5) but with a more frequent expression of CD11b, CD14, CD15 and less frequent of MPO. In univariate analysis CD19 (p=.04), CD34 (p=.02) and MPO (p<.001) retained statistical significance. 7) 20 (5.1%) with +8 were CD13+ in 95.6%, while the other markers were present in less than 80% of cases, in particular lower CD33+ blasts (p=.01). 8) 17 (4.3%) had 11q23abn, with CD13+<CD33+, frequent TdT+ (61.5%) and rare CD34+ (31.8%, p=.02). CD11c and CD14 were more frequently expressed than in other subtypes (86.4% and 36.4%, respectively). T-lymphoid markers were present in 36.4%. Univariate analysis showed a positive association between 11q23abn and presence of CD11c (p=.04) and CD14 (p=.05). 9) 115 (29.2%) with a normal karyotype had a dishomogeneous antigenic profile. CD2 (p=.002), CD11c (p=.04) and HLA-DR (p<.001) were the most discriminant markers. Using a multivariate discriminant analysis, we identified a discriminant function only for group 1) and group 2), based on CD11c/CD13/CD34/MPO/HLA-DR (sensitivity >99%, specificity 94.7%) and CD7/CD11c/CD19/CD56/MPO/HLA-DR (sensitivity 83.3%, specificity 94.5%), respectively. We conclude that in AML patients some cytogenetic abnormalities are associated with peculiar antigenic profiles. In patients with normal karyotype the heterogeneity of antigenic pattern may reflect underlined distinct molecular abnormalities.