Crescenzi Barbara, La Starza Roberta, Romoli Silvia, Beacci Donatella, Matteucci Caterina, Barba Gianluca, Aventin Ana, Marynen Peter, Ciolli Stefania, Nozzoli Chiara, Martelli Massimo Fabrizio, Mecucci Cristina
Hematology and Bone Marrow Trasplantation Unit, University of Perugia, Italy.
Haematologica. 2004 Mar;89(3):281-5.
The deletion of the long arm of chromosome 5 is common in myelodysplastic syndromes (MDS) but is not limited to the 5q- syndrome as it is also seen in acute myeloid leukemia (AML), where it is often associated with other karyotypic aberrations. The aim of this study was to investigate whether deletions of known suppressor sequences occur in myeloid malignancies associated with 5q-.
Thirty patients with MDS or AML were selected for the presence of a 5q karyotypic deletion, either isolated (19 cases) or associated with other chromosome changes (11 cases). Multiple fluorescent in situ hybridization (FISH) in interphase nuclei was applied in all cases using a panel of eleven probes for known suppressor genes or loci deleted in MDS/AML. Metaphase FISH was also performed to clarify discrepancies between conventional and molecular cytogenetics.
No additional deletions were found in nineteen cases with an isolated 5q-. Mono-allelic deletions where found in 9/11 cases, 3 of which were related to monosomies by conventional cytogenetics. Interphase-FISH showed p53, AML1, D13S25, NF1, or Ikaros in six out of nine (66%) patients with 5q- and additional karyotypic changes. Metaphase FISH was helpful in assigning some of these cryptic events to non-proliferating cells.
Our study emphasizes that isolated 5q- is the marker of a highly stable clone in both MDS and AML. AML with isolated 5q- are molecularly closer to 5q- syndrome than to AML with complex changes. Interphase-FISH data strongly support a mutator phenotype underlying complex karyotypes with a 5q deletion.
5号染色体长臂缺失在骨髓增生异常综合征（MDS）中很常见，但并不局限于5q-综合征，在急性髓系白血病（AML）中也可见到，且常与其他核型异常相关。本研究的目的是调查在与5q-相关的髓系恶性肿瘤中是否存在已知抑癌序列的缺失。
选择30例伴有5q核型缺失的MDS或AML患者，其中孤立性缺失（19例）或伴有其他染色体改变（11例）。所有病例均采用一组针对MDS/AML中已知缺失的抑癌基因或位点的11种探针，在间期核中进行多重荧光原位杂交（FISH）。还进行了中期FISH以澄清传统细胞遗传学和分子细胞遗传学之间的差异。
19例孤立性5q-患者未发现其他缺失。在11例中的9例发现单等位基因缺失，其中3例通过传统细胞遗传学与单体相关。间期FISH显示，在9例伴有5q-及其他核型改变的患者中有6例（66%）存在p53、AML1、D13S25、NF1或Ikaros基因缺失。中期FISH有助于将其中一些隐匿性事件归因于非增殖细胞。
我们的研究强调，孤立性5q-是MDS和AML中高度稳定克隆的标志物。伴有孤立性5q-的AML在分子水平上更接近5q-综合征，而不是伴有复杂改变的AML。间期FISH数据有力地支持了具有5q缺失的复杂核型背后的突变体表型。
