Double Minute Chromosome in Acute Myeloid Leukemia.

Introduction: Double minutes (dmin) are small chromatin particles that lack a centromere and represent a form of extrachromosomal gene amplification. They have been found in a variety of solid tumors but are rare in hematological malignancies. C-MYC and MLL are the most common genes amplified on the dmin in AML. Here we report a case of AML in which FISH did not demonstrate C-MYC or MLL gene amplification on the dmin.

Case Report: A seventy-seven-year-old man was diagnosed with acute leukemia. Histology and flow cytometry (blasts positive for CD13, CD33, CD34, HLA-DR, CD15, CD117 and cytoplasmic MPO) were consistent with M2 AML. Chromosome analysis revealed abnormal karyotype with hypodiploidy 42–44 and loss of chromosome 5, 7,13,17,18, and Y. Structural rearrangements involving chromosomes 2,7,11,19 and 20 in addition to 2 marker chromosomes and dmin. FISH did not reveal C-MYC gene amplification. FISH did reveal MLL gene amplification, but not on the dmin. The patient received induction chemotherapy, and expired on day 14 due to cardiac complications.

Discussion: Double minutes are a mechanism for upregulated oncogene expression. After the development of molecular technology, FISH, it became possible to identify the amplified gene. A previous review (Thomas et al. Double minute chromosomes in monoblastic (M5) and myeloblastic (M2) acute myeloid leukemia: two case reports and a review of literature. Am J Hematol 2004 Sep;77(1):55–61), found C-MYC to be amplified on the dmin in 25 cases, MLL was found to be amplified on the dmin in 5 cases, and only 3 cases in which neither gene was found to be amplified on the dmin. Double minutes are associated with advanced age at presentation, a more aggressive clinical course, poor outcome with therapy, and shortened survival. The survival in most cases is reported to be less than 12 months.