B Lymphoblastic Leukemia (ALL) Associated with Inv(3)(q21q26)/t(3;3)(q21;q26).
Daniela Hoehn, Su S Chen, Patrick A Lennon, L Jeffrey Medeiros, Pei Lin. University of Texas M.D. Anderson Cancer Center, Houston
Background: Inv(3)(q21q26) or t(3;3)(q21;q26) with disruption of EVI1/MDS1 gene is a recurrent cytogenetic aberration associated with a subset of myeloid neoplasms, such as acute myeloid leukemia, myelodysplastic syndromes, or myeloid blast phase of chronic myelogenous leukemia. Although a mouse model has implicated ectopic EVI1/MDS1 expression in the pathogenesis of ALL (Cuenco and Ren, Oncogene 23: 2004), no patients with ALL associated with inv(3)(q21q26) or t(3;3)(q21;q26) have been reported.
Design: We retrospectively reviewed our files from 1996 until the present for cases of ALL associated with inv(3)(q21q26) or t(3;3)(q21;q26) and identified 6 cases of B-ALL. In each case the abnormality was detected by conventional cytogenetics performed on bone marrow aspirates. EVI1/MDS1 gene disruption was confirmed using a commercially available FISH probe (EVI1 break apart probe, Keratech, Netherlands) in 2 cases tested. Peripheral blood and bone marrow aspirate smears (Wright Giemsa), and bone marrow clot and biopsy sections (H&E) were reviewed. Immunophenotypic data generated by multicolor flow cytometric immunophenotypic analysis was also reviewed.
Results: The patient ages ranged from 12 to 58 years. There were 3 men and 3 women. Morphologic review confirmed the presence of numerous blasts ranging from 19 to 93% (median 69%). Megakaryocytes were not increased and there was no morphologic evidence of dysplasia. Immunophenotyping confirmed that the blasts were of immature B-cell lineage, positive for CD19, CD22, CD79a, CD34 and TdT. CD13 and CD33 were also expressed in each case. Each patient had a complex karyotype (> 3 abnormalities with a median of 9) and the Philadephia chromosome was present in 2 patients. Five patients had inv(3)(q21q26) and 1 had t(3;3)(q21;q26). Inv(3)/t(3;3) was detected in the initial, pre-therapy sample in 2 patients and in post-therapy samples in 4 patients. Five patients died from B-ALL, 14-83 months after initial diagnosis. The 12-year-old patient is alive and free of disease 8 years after diagnosis.
Conclusions: Inv(3)(q21q26) or t(3;3)(q21;q26) can occur in B-ALL. Based on the number of B ALL cases at our institution, we estimate that inv(3)/t(3;3) occurs in ≤ 1% of all cases of B-ALL. All cases expressed CD13 and CD33. Based on the complexity of the karyotypes in these cases, we believe inv(3)/t(3;3) occurs in B ALL as a manifestation of general genetic instability.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 158, Wednesday Morning