Features of an Unusual AML with t(4;12)/Pdgra-ETV6 As the Sole Cytogenetic Abnormality Associated with Myelodysplastic Changes: A Case Report and Literature Review

The t(4;12) cytogenetic abnormality is rare in AML, and is associated with a unique morphologic and immunophenotypic profile. Pseudo-lymphoid morphology of myeloid blasts (appearing as atypical lymphocytes), multilineage dysplasia, absence of eosinophilia, aberrant CD7 and lack of myeloperoxidase (MPO) expression, low frequency of FLT3 mutations, and treatment refractoriness are some of the characteristics of this AML subtype previously described in the literature.

We report a case of AML with t(4;12) in a middle-age male who presented with pancytopenia: WBC 3.34 (65% lymphocytes), Hgb 6.9, Plt 13, and no known prior history of a myeloid neoplasm. Bone marrow aspirate revealed 78% blasts that appeared large with uneven chromatin distribution, prominent nucleoli, and inconspicuous granules; and significant dysplastic features in the erythroid and megakaryocyte elements. Immunostains performed on the trephine core biopsy showed blasts expressed CD34 (subset), CD71 (subset), and were CD117+ Bcl-2+ CD43+ CD7+ MPO-. Flow cytometry identified 74% myeloblasts, positive for CD34, CD38, CD123, CD117, CD33, HLA-DR, CD13 (subset), CD56, CD7, CD71; negative for monocyte-specific markers. The morphologic and immunophenotypic features were compatible with AML with MDS-related changes.

Karyotype analysis identified t(4;12)(q12;p13) in 18/20 cells, and no additional chromosomal abnormalities. PDGFRA translocation to 12p was confirmed using PDGFRA and ETV6 FISH probes. Analysis of frequent genomic alterations in AML identified BCOR p.Leu1646Profs, TET2 p.Gln1627Ilefs, U2AF1 p.Ser34Phe mutations; and no FLT3 mutation.

Conclusions: In AML with t(4;12)/PDGFRA-ETV6, though lack of a FLT3 mutation is relatively favorable, BCOR and U2AF1 mutations and multilineage dysplasia are unfavorable prognostic factors. Synergism of the additional oncogenic mutations with the PDGFRA activating mutation can be postulated. The t(4;12)/PDGFRA-ETV6 should be recognized in the WHO classification as a recurrent balanced translocation in AML with MDS-related changes.