Aberrant CD25 and Increased CD123 Expression Are Common in Acute Myeloid Leukemia with Partial Tandem Duplication and Are Associated with Internal Tandem Duplication.

[BACKGROUND] partial tandem duplication (PTD) occurs in approximately 5-10% of acute myeloid leukemia (AML) cases and is associated with poor prognosis. While its cytogenetic and molecular features are well described, the immunophenotypic characteristics of AML with -PTD remain incompletely defined.

[METHODS] We identified 47 cases of AML with -PTD by optical genome mapping. All cases underwent flow cytometric immunophenotypic analysis and next-generation sequencing using an 81-gene panel.

[RESULTS] The cohort included 32 men and 15 women with a median age of 67 years (range, 19-87). Thirty-eight cases were de novo AML, and nine were secondary to myelodysplastic syndrome and/or myeloproliferative neoplasm. Most cases (93%) demonstrated a normal or non-complex karyotype. The most frequent mutations involved (47%), (43%), and (23%). Thirty-one cases (66%) were granulocytic, while 16 (34%) showed granulocytic and/or monocytic differentiation. Blasts uniformly expressed HLA-DR and frequently expressed CD117 (91%) and CD34 (79%). Increased expression of CD123 (74%) and CD117 (43%) and decreased expression of HLA-DR (74%) and CD38 (69%) were common. Aberrant CD25 expression was observed in 51% of cases. Increased CD123 and aberrant CD25 expression were significantly associated with -ITD mutations (both < 0.0001) but not with other recurrent mutations. There was no correlation between -ITD mutation and expression levels of CD117, CD38 or HLA-DR (all > 0.05).

[CONCLUSIONS] AML with -PTD shows distinctive immunophenotypic features with increased CD123 and aberrant CD25 expression, both associated with -ITD. These markers may have diagnostic and therapeutic relevance in this AML subtype.