Molecular Analysis of a New Variant of the CBFβ - MYH11 Gene Fusion

Abstract

The inv(16)(p13q22) is observed in 16% of patients with acute myelogenous leukemia (AML). It is classically found in the AML M4Eo subtype, which has distinctive morphological abnormalities in the bone marrow including myelomonocytic differentiation and an increase in atypical bone marrow eosinophils. A gene fusion involving CBF &#103 and MYH11 is invariably created by the inv(16)(p13q22) and is thought to be a necessary genetic lesion in this form of leukemia. The most common fusion point occurs at CBF &#103 nucleotide (nt) 495 and MYH11 nt 1921; however, several rare variants have been described. We report a patient with AML M4Eo whose leukemic cells contained two distinct CBF &#103 - MYH11 transcripts, one rare and the other previously undescribed. Both gene fusion products were cloned and sequenced and the breakpoints were identified. These were at CBF &#103 nt 495 and MYH11 nt 994 and CBF &#103 nt 486 and MYH11 nt 1591. The CBF &#103 495 / MYH11 994 fusion is seen in 5-7% of AML M4Eo, while the CBF &#103 486 / MYH11 1591 fusion is novel. We postulate that these two fusions arose from a single rearranged chromosome 16 by way of alternative splicing. These fusions were associated with a good prognosis in this patient. Molecular diagnostic facilities should be aware of the existence of the CBF &#103 486 / MYH11 1591 variant and its potential association with the previously described type E fusion.

• Acute Myelogenous Leukemia
• Aml M4eo
• Fusion Transcript
• CBFβ - MYH11
• Alternative Splicing