Precursor B-Cell Acute Lymphoblastic Leukemia with RUNX1 (A.K.A. AML1) Amplification: A New Distinct Clinicopathologic Entity?
Kaaren K Reichard. Univ. of New Mexico, Albuquerque
Background: Precursor B-cell acute lymphoblastic leukemia (B-ALL) is a heterogeneous disease with several distinct genetic subgroups per the WHO 2008 classification. Each genetic subgroup is a unique clinicopathologic entity (e.g. B-ALL with BCR-ABL1). Undoubtedly, additional such genetic subgroups exist in B-ALL. We have identified cases of B-ALL with RUNX1 amplification which may constitute a new clinicopathologic entity with potential therapeutic implications.
Design: We identified 8 cases of pediatric B-ALL with RUNX1 (a.k.a. AML1) amplification out of 213 B-ALL total from our files (January 2001-2010). These cases are typically identified by "default" when using the FISH probe set to detect ETV6-RUNX1 (a.k.a. TEL-AML1) fusion but instead identify multiple copies of to assess for that specific cryptic fusion in B-ALL. We evaluated the clinical, laboratory, morphologic, immunophenotypic (IP), cytogenetic and outcome features of these 8 cases.
Results: The mean patient age was 8.1 years (range 3-15, median 11) with a M:F ratio of 7:1. The clinical presentations were typical for ALL including bone pain and fatigue. Lab studies showed low/normal WBC counts ranging from 1.7-13.7 x 109/L with peripheral blast percentages of 0-24% (median 11%). 6/8 patients were pancytopenic. Cerebrospinal fluid was negative in 7/7 cases. Bone marrow biopsies showed >90% blasts with typical lymphoblast morphology. 2/8 cases showed occasional cells with more abundant cytoplasm and a nucleolus. IP features showed a characteristic CD19+, CD10+, CD34+, TdT+, CD79a+, surface Ig(-) profile with 6/8 cases showing significant CD20 expression. Cytogenetics were abnormal in 4/6 cases with an adequate study. All patients were enrolled on a COG protocol. 6 of the 7 males are alive and free of disease (mean follow up 23 months). The remaining male patient was in complete remission at 72 months and then lost to follow up. The female patient was in first relapse and died of disease.
Conclusions: Genetic subgroups within B-ALL are well-known. They correlate with prognosis and often effect therapeutic regimens. Additional recurring genetic subgroups undoubtedly exist, particularly as more advanced molecular tests are routinely employed. We think that one such distinct clinicopathologic entity is B-ALL with RUNX1 amplification. In our cohort of 8 cases, the patients were predominantly male with low WBC counts, lack of cerebrospinal fluid involvement and good outcome. Further assessment of similar patients treated homogeneously will provide additional insight into this potential new B-ALL genetic subgroup.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 157, Wednesday Morning