Isolated Clonal Trisomy 13 in Philadelphia Chromosome-Negative Metaphases in Patients with Chronic Myelogenous Leukemia
C Cameron Yin, Shimin Hu, L Jeffrey Medeiros, Gary Lu. UT MD Anderson Cancer Center, Houston, TX
Background: The significance of chromosomal abnormalities in the Philadelphia chromosome (Ph)-negative metaphases of patients with chronic myelogenous leukemia (CML) has rarely been studied. We describe the clinicopathologic features of 4 patients with CML associated with isolated clonal trisomy 13 in Ph-negative metaphases.
Design: We searched our database for CML cases with isolated clonal trisomy 13 from January 1997 to September 2011. Clinical and laboratory data were obtained from the medical records. Peripheral blood and bone marrow specimens were reviewed. Conventional cytogenetics, fluorescence in situ hybridization (FISH), and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) were performed for the detection of t(9;22)(q34;q11)/BCR-ABL1 fusion transcript.
Results: We identified 4 CML patients with isolated clonal trisomy 13. There were 2 men and 2 women with a median age of 44 years (range, 42-64). All patients presented with left-shifted leukocytosis, basophilia, eosinophilia, and thromobocytosis. One patient had splenomegaly. Bone marrow biopsy specimens showed hypercellular bone marrow with left-shifted granulocytic hyperplasia, basophilia, eosinophilia, and atypical megakaryocytic hyperplasia. Blasts were not increased (median, 2%; range, 2-4%). All patients were treated with hydroxyurea and imatinib; 2 patients additionally received interferon and ara-c. All achieved complete cytogenetic remission. The median interval from initial diagnosis to the appearance of trisomy 13 clone was 73.5 months (range, 64-84). At the time of detection of trisomy 13, all patients had undetectable Ph by karyotypic analysis and FISH. qRT-PCR showed no (n=3) or low (n=1, BCR-ABL1/ABL1, 0.15) BCR-ABL1 fusion transcript. In 3 patients, the trisomy 13 clone was transient and disappeared after a median of 12 months (range, 5-12). With a median follow-up of 42 months (range, 20-85), none of these 3 patients developed any hematopoietic disorder. One patient developed Ph-negative acute myeloid leukemia at the time of the occurrence of trisomy 13, and died 1 month later.
Conclusions: Isolated clonal trisomy 13 occurs in Ph-negative metaphases in a small subset of CML patients. In most patients this abnormality is transient and of no known clinicopathologic consequence. However, in rare instances, it can reflect the emergence of a new neoplastic clone.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 216, Wednesday Morning