Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis.
Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1 and 11q22.3 have a very poor prognosis.
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DOI：
10.1111/bjh.12534
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发表时间：
2013-11
影响因子：
6.5
通讯作者：
Zent CS
中科院分区：
文献类型：
--
作者：
Greipp PT;Smoley SA;Viswanatha DS;Frederick LS;Rabe KG;Sharma RG;Slager SL;Van Dyke DL;Shanafelt TD;Tschumper RC;Zent CS
在慢性淋巴细胞白血病（CLL）患者中，通过荧光原位杂交（FISH）检测到17p13.1缺失（TP 53缺失）或11q22.3缺失（ATM缺失）与较差的预后相关。由于TP 53和ATM是TP 53通路的组成部分，我们假设17 p13.1-（17 p-）和11q22.3-（11 q-）发生在同一个细胞（克隆17 p-/11 q-）将赋予比17 p-或11 q-更差的预后。我们研究了2184例CLL患者的FISH（1995-2012），以确定17 p-，11 q-或克隆17 p-/11 q-的首次出现。20例（1%）患者具有克隆17 p-/11 q-，158例（7%）具有17 p-（包括4例具有17 p-和11 q-的单独克隆），247例（11%）具有11 q-，1759例（81%）既没有17 p-也没有11 q-。15例（73%）克隆性17 p-/11 q-患者中有11例存在功能失调的TP 53突变。克隆17 p-/11 q-的总生存期（1.9年）显著短于17 p-（3.1年，p = 0.04）、11 q-（4.8年，p = <0.0001）或17 p-和11 q-均不存在（9.3年，p = <0.0001）。因此，克隆17 p-/11 q-的预后明显更差，这表明TP 53和ATM的至少一个拷贝的丢失会导致更具侵袭性的疾病。使用ATM/TP 53组合FISH探针组可以识别这些非常高风险的患者。
Detection of a 17p13.1 deletion (loss of TP53) or 11q22.3 deletion (loss of ATM), by fluorescence in situ hybridization (FISH), in chronic lymphocytic leukaemia (CLL) patients is associated with a poorer prognosis. Because TP53 and ATM are integral to the TP53 pathway, we hypothesized that 17p13.1- (17p-) and 11q22.3- (11q-) occurring in the same cell (clonal 17p-/11q-) would confer a worse prognosis than either 17p- or 11q-. We studied 2184 CLL patients with FISH (1995–2012) for the first occurrence of 17p-, 11q-, or clonal 17p-/11q-. Twenty (1%) patients had clonal 17p-/11q-, 158 (7%) had 17p- (including 4 with 17p- and 11q- in separate clones), 247 (11%) had 11q-, and 1759 (81%) had neither 17p- nor 11q-. Eleven of 15 (73%) tested patients with clonal 17p-/11q- had dysfunctional TP53 mutations. Overall survival for clonal 17p-/11q- was significantly shorter (1.9 years) than 17p- (3.1 years, p = 0.04), 11q- (4.8 years, p = <0.0001), or neither 17p- nor 11q- (9.3 years, p = <0.0001). Clonal 17p-/11q- thus conferred significantly worse prognosis, suggesting that loss of at least one copy of both TP53 and ATM causes more aggressive disease. Use of an ATM/TP53 combination FISH probe set could identify these very-high risk patients.
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影响因子：
45.3
作者：
Skowronska, Anna;Parker, Anton;Stankovic, Tatjana
通讯作者：
Stankovic, Tatjana
DOI：
10.1182/asheducation-2010.1.481
发表时间：
2010-12-01
影响因子：
3
作者：
Stilgenbauer, Stephan;Zenz, Thorsten
通讯作者：
Zenz, Thorsten
影响因子：
45.3
作者：
Austen, Belinda;Skowronska, Anna;Stankovic, Tatjana
通讯作者：
Stankovic, Tatjana
影响因子：
11.5
作者：
Rossi, Davide;Cerri, Michaela;Gaidano, Gianluca
通讯作者：
Gaidano, Gianluca
影响因子：
20.3
作者：
Damle, RN;Wasil, T;Chiorazzi, N
通讯作者：
Chiorazzi, N