B-Lymphoblastic Leukemia with t(14;19)(q32;p13.1) Involves the IGH@ and EPOR Genes and Is Associated with an Aggressive Clinical Course
Jesse M Jaso, Victoria W Lu, C Cameron Yin, Ming Zhao, Lynne Abruzzo, M James You, L Jeffrey Medeiros, Gary Lu. University of Texas MD Anderson Cancer Center, Houston, TX
Background: B-lymphoblastic leukemia (B-ALL) with t(14;19)(q32;p13.1) has been rarely reported in the literature. We present the first description of the clinicopathologic features of B-ALL with t(14;19)(q32;p13.1).
Design: We searched for cases of B-ALL with t(14;19)(q32;p13.1) in our hospital database from 2007 to 2012. Clinical data were obtained from the medical records. Flow cytometric immunophenotyping was performed on bone marrow aspirate samples. Bacterial artificial chromosome clones for IGH@ and EPOR (Invitrogen, USA) were cultured in LB media. DNA was isolated using PureLinkTM HiPure Plasmid DNA Purification kit (Invitrogen, USA) and was labeled with SepctrumGreen-dUTP for IGH@ and SepctrumRed-dUTP for EPOR (Abbott Molecular, Downers Grove, IL, USA). A cut-off of 2.8% was used to define positivity for IGH@/EPOR rearrangement, which appears as a single fusion signal on der(14)t(14;19)(q32;p13.1).
Results: We identified 5 cases of B-ALL with t(14;19)(q32;p13.1), representing <1% of all B-ALL cases diagnosed within the study interval. There were 3 men and 2 women (median age, 41 years; range, 21-75 years). One patient had leukocytosis (361 K/µL), 5/5 had anemia (median hemoglobin, 8.6 g/dL, range, 8.4-11.0 g/dL), and 5/5 had thrombocytopenia (median, 22 K/µL, range, 12-90 K/µL). The bone marrow was hypercellular in all cases (median, 90%; range, 80-100%) with trilineage hypoplasia and increased blasts (median, 88%; range, 60-92%). Flow cytometric immunophenotyping showed a precursor-B immunophenotype with expression of CD9, CD10, CD19, CD22, CD34, CD38, HLA-DR, and TdT in all cases as well as CD20 (4/5), cytoplasmic IgM (4/5), cytoplasmic CD79a (3/5), CD13 (2/5) and CD33 (2/5). All cases were negative for BCR-ABL1 by FISH or RT-PCR. t(14;19) was detected at initial diagnosis in 3 patients and at relapse in 2 patients. It was the sole abnormality in 3 cases, and part of a complex clone in 2 cases. FISH identified IGH@/EPOR rearrangement in all cases. All patients underwent induction hyper-CVAD chemotherapy; 2 patients also underwent stem cell transplant. 4/5 patients achieved complete remission after induction, but all 4 relapsed (median time to relapse, 10.5 months). With a median follow-up of 12.3 months (range, 6.4-58.3 months), all patients had died of disease.
Conclusions: t(14;19)(q32;p13.1) is a rare recurrent cytogenetic abnormality in B-ALL. It is observed more commonly in young patients and is associated with a high blast count, an IGH@/EPOR fusion gene, and an aggressive clinical course.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 177, Tuesday Morning