Clinicopathologic and molecular characterization of myeloid neoplasms with isolated t(6;9)(p23;q34)

Int J Lab Hematol. 2017 Aug;39(4):409-417. doi: 10.1111/ijlh.12641. Epub 2017 Mar 20.

Abstract

Introduction: The t(6;9)(p23;q34);DEK-NUP214 [t(6;9)] abnormality is found in 0.7-1.8% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). FLT3-ITD mutations are detected in t(6;9) patients. The t(6;9) abnormality is associated with poor outcomes. We studied the clinicopathologic and molecular profiles of patients with AML/MDS carrying t(6;9).

Methods: We collected clinical data of nine patients with AML/MDS with isolated t(6;9) (median age = 41 years; male/female = 4/5) and genotyped DNAs using whole exome, Sanger, and targeted sequencing.

Results: Our cohort was characterized by frequent multilineage dysplasia (56%), absence of phospho-STAT3/STAT5 expression, presence of myeloid markers (CD13, CD33, CD34, CD117, HLA-DR) with an aberrant expression of CD7, and poor outcome (median survival of 20 months). Although basophilia has been described in association with t(6;9), we observed lack of marrow basophilia in our cohort. Molecularly, 83% (5/6) of patients with AML/MDS with t(6;9) were characterized by at least one somatic mutation. Among them, four patients showed multiple mutations. FLT3-ITD mutations were detected in 33% of patients (2/6); 80% (4/5) of mutant patients died even after hematopoietic stem cell transplantation.

Conclusion: Our data demonstrated that AML/MDS patients with t(6;9) have diverse molecular mutations regardless of the presence of FLT3 mutations, which may contribute to their poor survival outcomes.

Keywords: AML; MDS; t(6;9)(p23;q34).

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Bone Marrow / pathology
  • Chromosomes, Human, Pair 6*
  • Chromosomes, Human, Pair 9*
  • Exome
  • Female
  • Gene Duplication
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Mutation
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / mortality
  • Retrospective Studies
  • Tandem Repeat Sequences
  • Translocation, Genetic*
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • fms-Like Tyrosine Kinase 3