Structural rearrangements of chromosome 3 in 57 patients with acute myeloid leukemia: clinical, hematological and cytogenetic features

Hematol J. 2002;3(1):21-31. doi: 10.1038/sj.thj.6200143.

Abstract

Introduction: Structural rearrangements of chromosome 3q have been described in approximately 2% of patients with acute myeloid leukemia. Breakpoints are mainly located in the 3q21 and 3q26 regions but may occur elsewhere on chromosome 3. To determine the relationship between these breakpoints and the hematological parameters, including outcome of these patients, we analysed data from newly diagnosed adult AML patients with 3q rearrangements referred to our institution over a 15-year period.

Materials and methods: This retrospective study was conducted using data from 57 AML patients (median age: 64 years, range 19-82) with 3q rearrangements. Cytogenetic analysis was performed using standard techniques (RHG banding, FISH). Data concerning AML patients with 3q abnormalities were compared for outcome with those from patients with normal karyotype and from patients with 5q deletion, treated according to the same intensive protocols for the same time period.

Results: Patients with myeloid malignancy displaying 3q rearrangement were assigned to five subgroups, including those with: 3q21/q26 rearrangement; 3q21 alone, including t(1;3)(p36;q21); 3q26 alone, resulting in translocations involving multiple chromosome partners; t(3;5); 3q deletions. Among these patients, 37 were treated in AML chemotherapy trials. Complete remission was achieved in 43% (26/57) of cases. Five patients died early. Sixteen patients were resistant to induction chemotherapy. Median DFS and median OS were 4.5 and 8.8 months respectively. Relapse was observed in 34% of patients achieving CR. Comparison of the outcome of CR patients with that of patients presenting with normal karyotype (intermediate-risk) or complete/partial 5q deletion (high-risk) confirmed the very poor prognosis of patients carrying 3q chromosomal rearrangements.

Conclusion: These data confirm that 3q rearrangements at q21 or q26 are recurring chromosomal abnormalities in AML. Appearing frequently in combination with monosomy 7 and an abnormal megakaryopoiesis, patients with these abnormalities have a particularly poor prognosis.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Chromosome Breakage*
  • Chromosomes, Human, Pair 3*
  • Female
  • Gene Rearrangement
  • Humans
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / mortality
  • Male
  • Middle Aged
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Sequence Deletion
  • Survival Analysis
  • Translocation, Genetic

Substances

  • Antineoplastic Agents