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

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′CBFB^del) often poses a challenge for interpretation, and the clinical importance of 3′CBFB^del associated CBFBr remains largely unknown. We identified 16 AML patients with 3′CBFB^del, 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 5 days after diagnosis of AML, all 10 patients received chemotherapy and achieved remission initially. However, within 3 years, 5 (50%) patients had relapsed, of whom, 1 died and 4 received hematopoietic stem cell transplant. After a median follow-up of 76 months, 3 patients died and 8 were alive in complete remission. Our study shows that detection of 3′CBFB^del is not equivalent to unbalanced CBFB rearrangement, and therefore, an alternative confirmatory test is warranted. AML with 3′CBFB^del/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.