Newcomb E W, Thomas A, Selkirk A, Lee S Y, Potmesil M
Department of Pathology, New York University School of Medicine, New York, USA.
Cancer Res. 1995 May 15;55(10):2044-7.
A correlative study has been performed to delineate further the role of the Rb gene in the disease B-cell chronic lymphocytic leukemia (B-CLL). First, we examined DNAs from B cells from 140 B-CLL patients representing all Rai stages of disease for the loss of 13q14 using two microsatellite markers mapping distal to the Rb locus. Loss of heterozygosity (LOH) of D13S133 was infrequent, occurring in 5 of 140 (4%) patients. The frequency for LOH of D13S218 was 33 of 140 (24%) samples and was independent of Rai stage of disease. Rb protein was detected in 19 of 23 (83%) samples. Of 4 patients lacking detectable Rb gene expression, only one showed LOH of D13S218. Rb protein levels varied from undetectable to high in samples with or without LOH for D13S218, and the levels were also independent of Rai stage of disease. Our findings support the role of DBM on 13q14, rather than Rb, as the candidate tumor suppressor gene that is frequently targeted for deletion in B-CLL. In addition, the data suggest that other mechanism(s) contribute to altered Rb expression detected in one-fourth of B-CLL B-cells.
已进行了一项相关性研究，以进一步阐明Rb基因在B细胞慢性淋巴细胞白血病（B-CLL）疾病中的作用。首先，我们使用位于Rb基因座远端的两个微卫星标记，检测了140例代表疾病所有Rai分期的B-CLL患者B细胞的DNA中13q14的缺失情况。D13S133杂合性缺失（LOH）很少见，140例患者中有5例（4%）出现。D13S218的LOH频率为140个样本中的33例（24%），且与疾病的Rai分期无关。在23个样本中的19个（83%）检测到了Rb蛋白。在4例缺乏可检测到的Rb基因表达的患者中，只有1例显示D13S218的LOH。对于D13S218有或无LOH的样本，Rb蛋白水平从不可检测到高表达不等，且其水平也与疾病的Rai分期无关。我们的研究结果支持13q14上的DBM而非Rb作为候选肿瘤抑制基因的作用，该基因在B-CLL中经常成为缺失的靶点。此外，数据表明其他机制导致了在四分之一的B-CLL B细胞中检测到的Rb表达改变。
