Ottaggio Laura, Viaggi Silvia, Zunino Annalisa, Zupo Simona, Rossi Edoardo, Spriano Mauro, Abbondandolo Angelo, Ferrarini Manlio
Mutagenesis Laboratory, National Cancer Research Institute, largo Rosanna Benzi 10, 16132 Genoa, Italy.
Haematologica. 2003 Jul;88(7):769-77.
B-cell chronic lymphocytic leukemia (B-CLL) results from the accumulation of monoclonal CD5+ B cells. Despite its homogeneity at cellular level, B-CLL is clinically heterogeneous. Clinical studies indicate that CD38+ B-CLL are characterized by a more aggressive clinical course than are CD38- B-CLL. On the basis of these studies and considering the established correlation between specific chromosome aberrations and the clinical course of B-CLL, it is possible that CD38+ B-CLL cases are also characterized by specific subsets of chromosomal alterations.
Comparative genomic hybridization (CGH) was performed on purified B-cells from peripheral blood of 52 patients with B-CLL in order to detect chromosome imbalance. The immunophenotype of the patients, including CD38 expression, was also determined by flow cytometry. The results of CGH experiments were then compared with CD38 expression.
We found a clear correlation between the presence of chromosomal imbalances and CD38 expression: 13/16 CD38+ cases had chromosome imbalances, most of them (12/13) correlated with a poor prognosis. Among the CD38- B-CLL patients, only 8/36 displayed chromosome imbalances; the only three cases with loss in 13q as a single aberration, considered a good prognostic marker, were in this group. Moreover, we found that cytogenetic alterations were also more complex in the CD38+ B-CLL subset, since 9/10 with two or more aberrations were in the CD38+ group.
Collectively, the data reinforce the value of CD38 as a prognostic factor and indicate that genotypic/phenotypic features distinguish B-CLL subsets.
B 细胞慢性淋巴细胞白血病(B-CLL)由单克隆 CD5+ B 细胞积累所致。尽管在细胞水平上具有同质性,但 B-CLL 在临床上具有异质性。临床研究表明,CD38+ B-CLL 的临床病程比 CD38- B-CLL 更具侵袭性。基于这些研究,并考虑到特定染色体畸变与 B-CLL 临床病程之间已确立的相关性,CD38+ B-CLL 病例也可能具有特定的染色体改变亚群。
对 52 例 B-CLL 患者外周血中的纯化 B 细胞进行比较基因组杂交(CGH),以检测染色体失衡。还通过流式细胞术确定患者的免疫表型,包括 CD38 表达。然后将 CGH 实验结果与 CD38 表达进行比较。
我们发现染色体失衡的存在与 CD38 表达之间存在明显相关性:16 例 CD38+病例中有 13 例存在染色体失衡,其中大多数(12/13)与预后不良相关。在 CD38- B-CLL 患者中,只有 8/36 显示出染色体失衡;作为良好预后标志物的仅有的三例以 13q 缺失为单一畸变的病例在该组中。此外,我们发现细胞遗传学改变在 CD38+ B-CLL 亚群中也更为复杂,因为 10 例中有 9 例具有两个或更多畸变的病例在 CD38+组中。
总体而言,这些数据强化了 CD38 作为预后因素的价值,并表明基因型/表型特征可区分 B-CLL 亚群。