Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Mol Oncol. 2012 Oct;6(5):553-64. doi: 10.1016/j.molonc.2012.06.004. Epub 2012 Jul 14.
Chromosomal rearrangements affecting the MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemia. In this study, conventional cytogenetic, fluorescence in situ hybridization, and molecular genetic studies were used to characterize the type and frequency of MLL rearrangements in a consecutive series of 45 Portuguese patients with MLL-related leukemia treated in a single institution between 1998 and 2011. In the group of patients with acute lymphoblastic leukemia and an identified MLL fusion partner, 47% showed the presence of an MLL-AFF1 fusion, as a result of a t(4;11). In the remaining cases, a MLL-MLLT3 (27%), a MLL-MLLT1 (20%), or MLL-MLLT4 (7%) rearrangement was found. The most frequent rearrangement found in patients with acute myeloid leukemia was the MLL-MLLT3 fusion (42%), followed by MLL-MLLT10 (23%), MLL-MLLT1 (8%), MLL-ELL (8%), MLL-MLLT4 (4%), and MLL-MLLT11 (4%). In three patients, fusions involving MLL and a septin family gene (SEPT2, SEPT6, and SEPT9), were identified. The most frequently identified chromosomal rearrangements were reciprocal translocations, but insertions and deletions, some cryptic, were also observed. In our series, patients with MLL rearrangements were shown to have a poor prognosis, regardless of leukemia subtype. Interestingly, children with 1 year or less showed a statistically significant better overall survival when compared with both older children and adults. The use of a combined strategy in the initial genetic evaluation of acute leukemia patients allowed us to characterize the pattern of MLL rearrangements in our institution, including our previous discovery of two novel MLL fusion partners, the SEPT2 and CT45A2 genes, and a very rare MLL-MLLT4 fusion variant.
染色体重排影响 MLL 基因与高危儿科、成人和治疗相关的急性白血病相关。在这项研究中，使用常规细胞遗传学、荧光原位杂交和分子遗传学研究来描述 1998 年至 2011 年在一家机构接受治疗的连续 45 例 MLL 相关白血病葡萄牙患者的 MLL 重排类型和频率。在急性淋巴细胞白血病患者中，有明确的 MLL 融合伙伴，47%的患者存在 MLL-AFF1 融合，这是由于 t(4;11)。在其余病例中，发现了 MLL-MLLT3(27%)、MLL-MLLT1(20%)或 MLL-MLLT4(7%)重排。在急性髓细胞白血病患者中发现的最常见的重排是 MLL-MLLT3 融合(42%)，其次是 MLL-MLLT10(23%)、MLL-MLLT1(8%)、MLL-ELL(8%)、MLL-MLLT4(4%)和 MLL-MLLT11(4%)。在三名患者中，鉴定了涉及 MLL 和 septin 家族基因(SEPT2、SEPT6 和 SEPT9)的融合。最常识别的染色体重排是相互易位，但也观察到插入和缺失，有些是隐匿性的。在我们的系列中，无论白血病亚型如何，MLL 重排的患者均预后不良。有趣的是，1 岁或以下的儿童与年龄较大的儿童和成人相比，总体生存率有显著提高。在急性白血病患者的初始遗传评估中使用联合策略，使我们能够描述我们机构中 MLL 重排的模式，包括我们之前发现的两个新的 MLL 融合伙伴，SEPT2 和 CT45A2 基因，以及一种非常罕见的 MLL-MLLT4 融合变体。
