On Being Duped: Duplication of Chromosome 1 [Dup(1)(q21q32)] as the Sole Cytogenetic Abnormality In a Patient Previously Treated for AML

Cytogenetic studies are an important prognostic tool in the management of hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). While a nonrandom structural gain of 1q may be seen in MDS and AML, it is most commonly due to an unbalanced translocation usually in association with other chromosomal abnormalities. Duplication of the long arm of chromosome 1 [dup(1)(q21q32)] as the sole abnormality in nonlymphoid hematologic malignancies has only rarely been reported. As a result, very little is known about the clinical significance of this chromosomal abnormality. However, it has been suggested that this single aberration is predictive of an increased risk of clonal evolution and poor overall prognosis.

A then 55 year old male presented in June, 2002 with a CBC showing: WBC 36,300/ul (74% blasts with Auer rods), Hgb 7.0 gm/dl, MCV 98fl, platelets 61,000/ul. Bone marrow biopsy was 90% cellular with sheets of blasts. The blasts were positive for CD34, CD117, HLA-DR, CD13, MPO, CD56, and Tdt. A diagnosis of AML M2 was made. Cytogenetics showed 45,X,^-Y, t(8;21)(q22;q22). He underwent successful standard induction with “7+3” followed by consolidation with “5+2” and 4 cycles of high dose cytarabine. Subsequent bone marrows after induction and during consolidation showed no evidence of AML. The karyotype was 46,XY with no evidence of t(8;21) by FISH. He has had complete recovery of his blood counts, except for intermittent neutropenia. In May, 2004, G-banding of his bone marrow revealed the presence of a dup(1)(q21q32) as an isolated cytogenetic aberration for the first time. This finding was again seen on follow up studies in 2006, 2007, and 2009. His most recent evaluation in May 2010 showed WBC 5,500/ul (neutrophils 2,200/ul), Hgb 14.0 gm/dl, MCV 92fl, platelets 299,000/ul. Bone marrow biopsy was 40% cellular with trilineage hematopoiesis. The aspirate showed erythroid hyperplasia with megaloblastoid features. No dysplastic RBC or ring sideroblasts were seen. Cytogenetics showed 46,XY,dup(1)(q21q32)[15]/46,XY[5]. FISH for AML1/ETO t(8;21) and for abnormalities of chromosomes 5, 7, 8, and 20 were negative.

Dup(1q) has been reported as an isolated cytogenetic abnormality in a variety of MDS subtypes. It may be either a primary or secondary chromosomal aberration. It has been suggested that isolated dup(1q) in MDS is a harbinger of disease progression. Recent reports of MDS with either inverted dup(1)(q32 q21) or dup(1)(q21q32) of both chromosome 1 homologs showed no disease progression but had very short follow-up.

To our knowledge, this case is the first report of an acquired duplication dup(1)(q21q32) as the sole abnormality in a patient previously treated for AML. This duplication developed approximately 2 years after induction and consolidation chemotherapy. The involved clone is not the original leukemic clone since there is no evidence for t(8;21) or ^-Y. Six years later, there has been no evidence of progression to MDS or sAML. It is not known why our patient has shown such long survivorship after discovery of dup(1)(q21q32), nor is it known if this chromosomal finding is a treatment related phenomenon. This case suggests that dup(1q) may not be exclusively associated with a poor prognosis. FISH analysis with a 1q21 probe is planned to confirm our G-banding observation.

Lachant: sanofi-aventis: Speakers Bureau; glaxosmithkline: Speakers Bureau.