Novel Chromosomal Aberration as Evidence of Clonal Evolution in a Case of Relapsed Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a heterogeneous group of diseases with a multitude of molecular genetic aberrations and variable clinical outcome. Clonal chromosomal abnormalities have been identified in over 50% of AML cases, and have been regarded as one of the most important prognostic markers. We present a case of a 28-year-old Caucasian woman with AML without maturation, diploid karyotype, that was resistant to multiple chemotherapies and relapsed after matched unrelated stem cell transplantation. Conventional cytogenetic analysis performed on bone marrow specimens revealed 46,XX,t(2;16)(p21;p11.2),t(11;14)(p13;p11.2). The t(11;14)(p13;p11.2) was confirmed by fluorescence in situ hybridization using a whole chromosome paint probe for chromosome 11. Morphologically, the bone marrow was hypercellular with trilineage hypoplasia and 84% blasts. Flow cytometry analysis showed that the blasts were of myeloid immunophenotype. Molecular studies detected internal tandem duplication of the FLT3 gene and a mutation in exon 12 of the NPM1 gene. The patient then received monotherapy with AC220, achieved a brief remission, and died of relapsed disease 23 months after initial diagnosis. This