3'CBFB deletion in CBFB-rearranged acute myeloid leukemia retains morphological features associated with inv(16), but patients have higher risk of relapse and may require stem cell transplant.

Abstract

Fluorescence in situ hybridization analysis (FISH) using a CBFB breakapart probe is widely used to detect CBFB rearrangement (CBFBr) in cases of acute myeloid leukemia (AML). However, detection of 3'CBFB deletion (3'CBFBdel) often poses a challenge for interpretation, and the clinical importance of 3'CBFBdel associated CBFBr remains largely unknown. We identified 16 AML patients with 3'CBFBdel, 11 (69%) of which were confirmed to have CBFB::MYH11 fusion. These 11 patients presented with de novo AML; 10 showed myelomonocytic differentiation, 8 had a prominent eosinophilic component, and 7 showed characteristic eosinophils with basophilic granules. Next generation sequencing showed mutations in 7/8 patients, 5 with KRAS/NRAS, 3 with FLT3-TKD, but none with KIT mutations. Except for one patient who died 5days after diagnosis of AML, all 10 patients received chemotherapy and achieved remission initially. However, within 3years, 5 (50%) patients had relapsed, of whom, 1 died and 4 received hematopoietic stem cell transplant. After a median follow-up of 76months, 3 patients died and 8 were alive in complete remission. Our study shows that detection of 3'CBFBdel is not equivalent to unbalanced CBFB rearrangement, and therefore, an alternative confirmatory test is warranted. AML with 3'CBFBdel/CBFBr often shows similar pathological features to AML with inv(16), but appears to have different mutation profiles and a higher risk of relapse requiring hematopoietic stem cell transplant.