Department of Clinical and Experimental Medicine, University of Perugia, Italy.
Br J Haematol. 2010 Apr;149(1):70-8. doi: 10.1111/j.1365-2141.2009.08056.x. Epub 2010 Jan 11.
Metaphase (M-) and array (A-) Comparative Genomic Hybridization (CGH) were used to investigate 40 cases of T- and 32 of B-cell acute lymphoblastic leukaemia (ALL) with normal/failed cytogenetics. M-CGH was performed in all cases and A-CGH in 10/12 T-ALL cases with uncertain/normal M-CGH results. M-CGH was abnormal in 38/72 cases, with a total of 110 imbalances (60 gains, 50 losses). 25/40 patients with T-ALL (62.5%) showed 77 imbalances, with at least 1 genomic imbalance and a mean of 3 aberrations/patient (range 1-12). 13/32 patients with B-ALL (40.6%) presented 34 imbalances, with a mean of 2.6 imbalances (range 1-8). A-CGH detected 4 more T-ALL cases with genomic imbalances. A-CGH identified NF1/17q11.2 deletion and interphase fluorescence in situ hybridization provided a 10.8% estimated overall incidence of NF1/17q11.2 deletion in T-ALL. In all but one case (6/7) with NF1 deletion, denaturing high-performance liquid chromatography and direct sequencing detected NOTCH1 gene mutations. Three or more imbalances in CGH-positive cases were significantly associated with resistance to treatment and death during or after induction therapy. We suggest that the work-up for ALL at diagnosis should include CGH investigations, particularly when cytogenetics is uninformative, because they may provide potentially valuable information with prognostic and therapeutic implications.
采用中期（M-）和阵列（A-）比较基因组杂交（CGH）分析 40 例 T 细胞和 32 例 B 细胞急性淋巴细胞白血病（ALL）患者的正常/失败细胞遗传学。所有病例均进行 M-CGH，12 例 T-ALL 中不确定/正常 M-CGH 结果的 10 例进行 A-CGH。M-CGH 异常 38/72 例，总共有 110 个不平衡（60 个增益，50 个丢失）。40 例 T-ALL 中有 25 例（62.5%）显示 77 个不平衡，至少有 1 个基因组不平衡，平均每个患者 3 个异常（范围 1-12）。32 例 B-ALL 中有 13 例（40.6%）呈现 34 个不平衡，平均有 2.6 个不平衡（范围 1-8）。A-CGH 检测到 4 例 T-ALL 患者有基因组不平衡。A-CGH 确定 NF1/17q11.2 缺失，间期荧光原位杂交提供了 T-ALL 中 NF1/17q11.2 缺失的 10.8%的估计总发生率。在所有有 NF1 缺失的病例中（6/7），除一个病例外，变性高效液相色谱法和直接测序检测到 NOTCH1 基因突变。CGH 阳性病例中出现 3 个或更多的不平衡与诱导治疗期间或之后的治疗抵抗和死亡显著相关。我们建议在诊断时 ALL 的检查应包括 CGH 研究，特别是当细胞遗传学无意义时，因为它们可能提供潜在有价值的信息，具有预后和治疗意义。
