PB1770 RARE VARIANTS OF CBFB‐MYH11 TRANSCRIPTS IN ACUTE MYELOID LEUKEMIA: CONTRIBUTION WITH 3 CASES
Authors: G. Balatzenko, S. Ivanova, B. Spassov, E. Hadjiev, G. Tsvetkova, V. Grklanov, A. Stoyanova‐Deleva, M. Guenova
Journal: HemaSphere (2019)

Background: Acute myeloid leukemia (AML) with inv(16)(p13.1q22)/t(16;16)(p13.1;q22) and/or the respective CBFB‐MYH11 rearrangements is a distinct subtype of AML characterized by the presence of abnormal eosinophil population in the bone marrow and “favorable” prognosis. At molecular level, more than 10 different CBFB‐MYH11 fusion genes and transcripts have been reported so far. The most frequently detected variant is type A transcripts, which accounts for approximately 85% of the CBFB‐MYH11 ‐positive cases. The remaining variants are rare and therefore their incidence, association with clinical and laboratory features and response to therapy are largely unknown. Aims: To determine the incidence and main characteristics of CBFB‐MYH11 ‐positive Bulgarian AML patients (pts) with rare types of fusion transcripts Methods: During a 15‐years period bone marrow aspirates of 856 AML pts, both adults and children, were tested for the main fusion transcripts in the Laboratory of Cytogenetics and Molecular Biology of the National Specialized Hospital for Active Treatment of Hematological diseases – Sofia, Bulgaria. Screening for CBFb‐MYH11 fusion transcripts was carried‐out by Reverse Transcription Polymerase Chain Reaction (RT‐PCR) using a protocol recommended by BIOMED‐1 Concerted Action. Results: Overall, CBFb‐MYH11 fusion transcripts were found in 49 (5.7%) pts, including 47 adults (95.9%) [42 with de novo AML (dnAML); 3 with therapy‐related AML, and 2 CBFb‐MYH11‐ positive myeloid blast crisis of BCR‐ABL1 ‐positive chronic myeloid leukemia (BC CML)] and 2 children (4.1%). Typical type A CBFb‐MYH11 transcripts were found in 46 pts (93.9%). In the remaining 3 (6.1%) cases, rare variants of transcripts (2 type D; 1 type B) were seen: (1) in a 41‐year old woman with dnAML; (2) in a 8‐year old girl with dnAML, and (3) in a 33‐year old male patient with primary BC CML. All pts presented with leukocytosis (32/29/474x10 9 /l); and anemia (Hb 77/104/111 g/l). In addition, in dnAML cases (#1,#2) was observed thrombocytopenia (8/53x10 9 /l), while in BC CML patient was found mild thrombocytosis (474x10 9 /l). No hepatosplenomegaly was found in dnAML cases. Blast cell bone marrow involvement varied from &gt;90% (#1) to 53%/32% (#2;#3). In 2 pts (#1,#2), blast cells were with myelomonocytic characteristics, while the BC CML (#3) corresponded to AML with maturation. Immunophenotyping revealed CD34‐expression in all cases, with aberrant co‐expression of CD19 in 2 of them (#1,#2). Molecular screening for D816 c‐KIT mutation was negative in both tested cases (#1;#3). Complete remission with a measurable residual disease level below 0.1% was achieved in both dnAML pts after standard chemotherapy (7+3) (#1) or induction according to the AML BFM protocol (#2). Hoewever, a relapse was registered 1 year later in patient #1, treated with FLAG‐IDA that resulted in heavy aplasia, complicated with a fatal hemorrhagic shock. The BC CML patient (#3) received AML chemotherapy in combination with imatinib, and the BCR‐ABL1/ABL1 level was 3.6% (IS), with 0.1% CBFb‐MYH11 transcripts at the 4th month. Summary/Conclusion: Rare CBFb‐MYH11 transcripts variants are very rare and account for 0.35% of AML Bulgarian patients. Presentation of these cases is highly variable, including de novo AML both in adults and children, as well as a primary BC of CML. However, they seem to be responsive to routine therapeutic protocols.