Acute Myeloid Leukemia with Rare T(16;21)(Q24;Q22) and RUNX1::CBFA2T3 Fusion Resembling AML with RUNX1::RUNX1T1: A Case Report and Literature Review

Document Type

Conference Proceeding

Publication Date

6-1-2024

Publication Title

J Mol Diagn

Abstract

Introduction: The t(16;21)(p24;q22) is an uncommon chromosomal abnormality, identified in approximately 1% of acute myeloid leukemia (AML) cases. A total of 77% of adult AML cases with t(16;21) are therapy related. Two different types have been observed, which result in FUS::ERG fusion (t(16;21)(p11;q22)) and RUNX1::CBFA2T3 fusion (t(16;21)(q24;q22), respectively. About half of these cases have additional cytogenetic aberrations commonly involving chromosomes 8 and 10. T(16;21)-associated acute leukemias exhibit morphologic and immunophenotypic features reminiscent of AML with t(8:21) rearrangement. It has been reported that patients harboring t(16;21) (q24;q22) exhibit a favorable response to AML-type treatments, suggesting management similar to AML with t(8;21)(q22;q22). We present a case of therapy-related acute leukemia with bi-phenotypic antigen profile (B/myeloid) and t(16;21)(q24;q22) (RUNX1::CBFA2T3), and summarize the cytogenetic and molecular findings. Methods: A 55-year-old female with history of stage IIIC grade 3 serous ovarian carcinoma, status post neoadjuvant chemotherapy, presented with B-symptoms and pancytopenia. Initial work-up included a peripheral blood smear which showed 73% blasts. Additional work-up with bone marrow biopsy, immunohistochemistry, flow cytometry, chromosome analysis, fluorescence in-situ hybridization (FISH), and next generation sequencing was performed for final diagnosis and classification. Results: Bone marrow exam showed 56% blasts which were intermediate-sized to large cells with round to irregular nuclei, fine chromatin, prominent nucleoli, and cytoplasmic granules. The blasts were positive for CD34, CD117, CD13, CD33, MPO, and bright CD19, cyto CD79a, and PAX5, compatible with a diagnosis of acute leukemia with B/myeloid. Chromosomal analysis showed an abnormal karyotype of 46,XX,add(7)(q21),t(16;21)(q24;q22), suggesting loss of 7q. FISH analysis was significant for gain of chromosome 21 involving the RUNX1 probe region (89.5% of nuclei having 3 copies of RUNX1 probe region) and no evidence of t(8;21). Gene sequencing studies identified RUNX1::CBFA2T3 fusion as well as KRAS G12D, a recurrent pathogenic variant in AML and acute lymphoblastic leukemia. In addition, loss of EZG2, BRAF, and CUX1 was observed, suggesting loss of 7q, in concordance with cytogenetic findings. The patient was treated with Vyxeos chemotherapy, and results from repeat bone marrow biopsy on day 14 were consistent with disease remission. Conclusions: This case highlights the rarity and significance of translocation t(16;21) in myeloid neoplasms and therapy-related myeloid neoplasms. Further research on larger cohorts of patients with t(16;21) is warranted to establish the prognostic implications and optimum treatment for these patients.

Volume

26

Issue

6

First Page

S28

Last Page

S29

Find It @ Sladen

Share

COinS