Lee Jeong N, Giles Fancis, Huh Yang O, Manshouri Taghi, O'Brien Susan, Kantarjian Hagop M, Keating Michael J, Albitar Maher
Departments of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4095, USA.
Eur J Haematol. 2003 Oct;71(4):235-42. doi: 10.1034/j.1600-0609.2003.00089.x.
The genetic events involved in the transformation of chronic lymphocytic leukemia (CLL) to Richter's syndrome (RS) are poorly understood. Frequently large cells are seen in the bone marrows of patients with CLL and evidence of RS. Using a laser-capture microdissection we analyzed small and large leukemic bone marrow cells from 19 patients with RS for loss of heterozygosity (LOH) on chromosome 11 (D11S2179 at the ATM gene), 17 (D17S938 and D17S1852 at the TP53 site), and 20 (Plc1, D20S96, D20S110, and D20S119). Megakaryocytes were also isolated and used as a control for normal cells. Four of 15 (27.7%) informative cases showed LOH in small cells in the ATM gene while seven (46.7%) showed LOH in large cells. Six of 15 (40%) informative cases had LOH in chromosome 17 in small cells, and eight (53%) showed LOH in large cells. Eleven of 19 informative cases (61.1%) showed LOH in chromosome 20 in large cells, and eight (42.1%) showed LOH in small cells. RS cases with LOH at chromosome 20 were associated with marginally shorter survival rates (P = 0.08). Our data suggest that there are significant molecular differences between large and small cells in patients with CLL. Further analysis of the genes on these chromosomes may provide new insight into our understanding of the transformation of small CLL cells to large (Richter) cells.
慢性淋巴细胞白血病（CLL）转化为里氏综合征（RS）所涉及的基因事件目前尚不清楚。在CLL患者和RS患者的骨髓中经常能看到大细胞。我们使用激光捕获显微切割技术，分析了19例RS患者的小的和大的白血病骨髓细胞，检测其11号染色体（ATM基因处的D11S2179）、17号染色体（TP53位点处的D17S938和D17S1852）和20号染色体（Plc1、D20S96、D20S110和D20S119）上的杂合性缺失（LOH）情况。巨核细胞也被分离出来作为正常细胞的对照。15例信息充分的病例中，有4例（27.7%）在小细胞的ATM基因中显示杂合性缺失，而7例（46.7%）在大细胞中显示杂合性缺失。15例信息充分的病例中，有6例（40%）在小细胞的17号染色体中显示杂合性缺失，8例（53%）在大细胞中显示杂合性缺失。19例信息充分的病例中，有11例（61.1%）在大细胞的20号染色体中显示杂合性缺失，8例（42.1%）在小细胞中显示杂合性缺失。20号染色体存在杂合性缺失的RS病例的生存率略短（P = 0.08）。我们的数据表明，CLL患者的大细胞和小细胞之间存在显著的分子差异。对这些染色体上基因的进一步分析可能会为我们理解小的CLL细胞向大的（里氏）细胞转化提供新的见解。
