Osman Afaf, Gocke Christopher D, Gladstone Douglas E
Departments of Oncology and Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
Departments of Oncology and Pathology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
Clin Lymphoma Myeloma Leuk. 2017 Feb;17(2):97-99. doi: 10.1016/j.clml.2016.11.008. Epub 2016 Nov 21.
Fluorescence in situ hybridization and immunoglobulin (Ig) heavy-chain variable-region (IgHV) mutational status are used to predict outcome in chronic lymphocytic leukemia (CLL). Although DNA aberrations change over time, IgHV sequences and mutational status are considered stable.
In a retrospective review, 409 CLL patients, between 2008 and 2015, had IgHV analysis: 56 patients had multiple analyses performed. Seven patients' IgHV results changed: 2 from unmutated to mutated and 5 from mutated to unmutated IgHV sequence.
Three concurrently changed their variable heavy-chain sequence. Secondary to allelic exclusion, 2 of the new variable heavy chains produced were biologically nonplausible.
The existence of these new nonplausible heavy-chain variable regions suggests either the CLL cancer stem-cell maintains the ability to rearrange a previously silenced IgH allele or more likely that the cancer stem-cell produced at least 2 subclones, suggesting that the CLL cancer stem cell exists before the process of allelic exclusion occurs.
荧光原位杂交和免疫球蛋白（Ig）重链可变区（IgHV）突变状态用于预测慢性淋巴细胞白血病（CLL）的预后。尽管DNA畸变会随时间变化，但IgHV序列和突变状态被认为是稳定的。
在一项回顾性研究中，对2008年至2015年间的409例CLL患者进行了IgHV分析：56例患者进行了多次分析。7例患者的IgHV结果发生了变化：2例从未突变变为突变，5例从突变变为未突变的IgHV序列。
3例同时改变了其可变重链序列。由于等位基因排斥，产生的2条新可变重链在生物学上不合理。
这些新的不合理重链可变区的存在表明，要么CLL癌症干细胞保持重新排列先前沉默的IgH等位基因的能力，要么更有可能的是癌症干细胞产生了至少2个亚克隆，这表明CLL癌症干细胞在等位基因排斥过程发生之前就已存在。
