AML with Translocation T(8;16) Shows Unique Cytomorphological, Cytogenetic, Molecular, and Prognostic Features and Therefore Qualifies as An Own Entity According to WHO Criteria

• Published in: Blood 2008-11, Vol.112 (11), p.1197-1197
• Main Authors: Kohlmann, Alexander, Dugas, Martin, Klein, Hans-Ulrich, Ruckert, Christian, Kern, Wolfgang, Schnittger, Susanne, Löffler, Helmut, Haferlach, Claudia, Haferlach, Torsten
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V112.11.1197.1197

Balanced chromosomal rearrangements define distinct biological subsets in acute myeloid leukemia (AML). It is recognized that recurrent balanced aberrations, such as t(15;17), t(8;21), inv(16), and 11q23/MLL translocations, show a close correlation to cytomorphology and also harbor specific gene expression signatures. We here present a cohort of 13 AML cases with t(8;16)(p11;p13). This translocation is rare with only 13 cases (6 males, 7 females) diagnosed from our overall cohort of 6124 cases of AML over recent years, and is more frequently found in therapy-related AML than in de novo AML (7/438 t-AML, and 6/5686 de novo, p=0.00001). Prognosis was poor with median overall survival of 4.7 months. Five patients deceased within the first month after diagnosis. AML with t(8;16) is characterized by striking cytomorphologic features: In all 13 cases the positivity for myeloperoxidase (MPO) on bone marrow smears was >30% (median: 85%) and intriguingly, in parallel also >40% (median: 88%) of blast cells stained strongly positive for non-specific esterase (NSE) in the same cell, suggesting that AML with t(8;16) arise from a very early stem cell with both myeloid and monoblastic differentiation potential. Therefore, AML with t(8;16) cases can not be classified according to standard FAB categories. Morphologically we also detected erythrophagocytosis in 7/13 cases, a specific feature in AML with t(8;16) that was previously described. With respect to cytogenetics, 6/13 patients had t(8;16)(p11;p13) as sole abnormality. 7/13 patients demonstrated additional non-recurrent abnormalities, 4 cases with single additional aberrations, and 3 cases with two or more additional aberrations. Molecular analyses detected the MYST3- CREBBP fusion transcript in all cases tested (12/12). We then compared gene expression patterns in 7 cases of AML with t(8;16) to: (i) AML FAB subtypes M1 and M4/5 with strong MPO or NSE with normal karyotype and to (ii) distinct AML subtypes with balanced chromosomal aberrations according to WHO classification. In a first series using Affymetrix HG-U133A+B microarrays 4 cases of AML with t(8;16) were compared to FAB M1 (n=46), M4 (n=41), M5a (n=9), and M5b (n=16). Hierarchical clustering and principal component analyses revealed that AML with t(8;16) were intercalating rather with FAB subtypes M4 and M5b and did not cluster near to FAB M1, although strong positivity for MPO was seen in all t(8;16) cases. Thus, monocytic characteristics influence the ge