Stulberg Jennifer, Kamel-Reid Suzanne, Chun Kathy, Tokunaga Jason, Wells Richard A
Department of Cellular and Molecular Biology, Ontario Cancer Institute, Toronto, Ont., Canada.
Leuk Lymphoma. 2002 Oct;43(10):2021-6. doi: 10.1080/1042819021000015989-1.
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 CBFbeta 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 CBFbeta 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 CBFbeta-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 CBFbeta nt 495 and MYH11 nt 994 and CBFbeta nt486 and MYH11 nt 1591. The CBFbeta(495)/MYH11(994) fusion is seen in 5-7% of AML M4Eo, while the CBFbeta(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 CBFbeta(486)/MYH11(1591) variant and its potential association with the previously described type E fusion.
16%的急性髓系白血病（AML）患者存在inv(16)(p13q22)。经典情况下，它见于AML M4Eo亚型，该亚型在骨髓中有独特的形态学异常，包括髓单核细胞分化以及非典型骨髓嗜酸性粒细胞增多。inv(16)(p13q22)总是会产生一种涉及CBFβ和MYH11的基因融合，并且被认为是这种白血病形式中必要的遗传损伤。最常见的融合点出现在CBFβ核苷酸（nt）495和MYH11 nt 1921处；然而，也描述了一些罕见变体。我们报告了一名AML M4Eo患者，其白血病细胞包含两种不同的CBFβ-MYH11转录本，一种罕见，另一种此前未被描述。两种基因融合产物均被克隆和测序，并确定了断点。这些断点分别位于CBFβ nt 495和MYH11 nt 994以及CBFβ nt486和MYH11 nt 1591处。CBFβ(495)/MYH11(994)融合见于5%-7%的AML M4Eo患者，而CBFβ(486)/MYH11(1591)融合是新发现的。我们推测这两种融合是由一条重排的16号染色体通过可变剪接产生的。这些融合与该患者的良好预后相关。分子诊断机构应了解CBFβ(486)/MYH11(1591)变体的存在及其与先前描述的E型融合的潜在关联。
