Lai J L, Preudhomme C, Zandecki M, Flactif M, Vanrumbeke M, Lepelley P, Wattel E, Fenaux P
Service de Cytogénétique, C.H.U., Lille, France.
Leukemia. 1995 Mar;9(3):370-81.
We looked for correlations between cytogenetic rearrangements leading to 17p deletion and presence of dysgranulopoïesis and p53 mutations in MDS and AML. Forty-nine (4.3%) of the MDS and AML studied cytogenetically at our institution over a period of 11 years had detectable 17p deletion, through monosomy 17 (14 cases) or rearrangements of chromosome 17 (generally unbalanced translocations between 17p and another chromosome) (35 cases). Most of the patients had additional complex cytogenetic findings, and 10 cases were therapy related. In 70% of the patients with 17p deletion, a particular type of dysgranulopoïesis, combining pseudo-Pelger-Huët anomaly and small vacuolated neutrophils was seen in > 5% marrow neutrophils, whereas 69% of the patients had a p53 mutation, generally in a missense mutation involving exons 5 to 8 of the p53 gene. FISH analysis, performed in eight cases, confirmed loss of one P53 allele in all of them. No DNA fragmentation suggesting increased apoptosis was found in marrow samples. Response to chemotherapy was almost uniformly poor and median survival was only 3 months. Analysis of dysgranulopoïesis and p53 mutations were also made in 'control' groups of MDS and AML without 17p deletion. 'Typical' dysgranulopoïesis, combining pseudo-Pelger-Huët anomaly and small vacuolated neutrophils in > 5% marrow neutrophils, was not seen in any of the 47 MDS and AML without 17p deletion analyzed and without p53 mutation (P = 10(-4) with patients having 17p deletion), and was seen in one of five patients without 17p deletion but with a p53 mutation. Only 3.1% of 256 MDS and AML without 17p deletion had a p53 mutation (P = 10(-4) with patients having 17p deletion). These findings suggest that 17p deletion, in MDS and AML, is strongly correlated to the presence of a particular type of dysgranulopoïesis and to a high incidence of p53 mutations, and that MDS and AML with 17p deletion could constitute a new morphological-cytogenetic-molecular entity in myeloid disorders.
我们研究了骨髓增生异常综合征（MDS）和急性髓系白血病（AML）中导致17p缺失的细胞遗传学重排与粒细胞生成异常及p53突变之间的相关性。在我们机构11年间进行细胞遗传学研究的MDS和AML患者中，49例（4.3%）通过17号染色体单体（14例）或17号染色体重排（通常为17p与另一染色体之间的不平衡易位）（35例）检测到17p缺失。大多数患者还有其他复杂的细胞遗传学发现，10例与治疗相关。在70%的17p缺失患者中，在超过5%的骨髓中性粒细胞中可见一种特殊类型的粒细胞生成异常，即假性Pelger-Huët异常与小空泡中性粒细胞并存，而69%的患者存在p53突变，通常为涉及p53基因外显子5至8的错义突变。对8例患者进行的荧光原位杂交（FISH）分析证实，所有患者均有一个P53等位基因缺失。在骨髓样本中未发现提示凋亡增加的DNA片段化现象。对化疗的反应几乎都很差，中位生存期仅3个月。我们还对无17p缺失的MDS和AML“对照组”进行了粒细胞生成异常和p53突变分析。在分析的47例无17p缺失且无p53突变的MDS和AML患者中，均未见到“典型”的粒细胞生成异常，即假性Pelger-Huët异常与小空泡中性粒细胞在超过5%的骨髓中性粒细胞中并存（与有17p缺失的患者相比，P = 10⁻⁴），在5例无17p缺失但有p53突变的患者中，有1例出现这种情况。在256例无17p缺失的MDS和AML患者中，只有3.1%有p53突变（与有17p缺失的患者相比，P = 10⁻⁴）。这些发现表明，在MDS和AML中，17p缺失与一种特殊类型的粒细胞生成异常的存在以及p53突变的高发生率密切相关，并且有17p缺失的MDS和AML可能构成髓系疾病中的一种新的形态学-细胞遗传学-分子实体。
