Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06.
Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06.
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DOI：
10.3324/haematol.2020.252825
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发表时间：
2021-10-01
期刊：
影响因子：
10.1
通讯作者：
Rambaldi A
中科院分区：
文献类型：
--
作者：
Caprioli C;Lussana F;Salmoiraghi S;Cavagna R;Buklijas K;Elidi L;Zanghi' P;Michelato A;Delaini F;Oldani E;Intermesoli T;Grassi A;Gianfaldoni G;Mannelli F;Ferrero D;Audisio E;Terruzzi E;De Paoli L;Cattaneo C;Borlenghi E;Cavattoni I;Tajana M;Scattolin AM;Mattei D;Corradini P;Campiotti L;Ciceri F;Bernardi M;Todisco E;Cortelezzi A;Falini B;Pavoni C;Bassan R;Spinelli O;Rambaldi A
骨髓增生异常或骨髓增殖性疾病后的继发性急性髓系白血病（sAML）是目前通过临床病史或特定形态学和细胞遗传学异常确定的高危类别。然而，在缺乏这些特征的情况下，识别某些病例（否则定义为新发 AML）的次要性质的不确定性仍然存在。为了测试染色质剪接体 (CS) 突变特征是否可以更好地定义新发 AML 组，我们分析了 413 名新诊断的 AML 患者的前瞻性队列，这些患者参加了一项随机临床试验 (NILG AML 02/06)，并提供了样本以进行准确的细胞遗传学和分子表征。在临床定义的新发 AML 中，17.6% 携带 CS 突变（CS-AML），并表现出更接近 sAML 的临床特征（年龄较大、白细胞计数较低和多系发育不良发生率较高）。该组的结果是不利的，与 sAML 相比与新发 AML 更相似（总生存期，CS-AML 为 30%，sAML 为 17%，而新发 AML 为 61%，P<0.0001；无病生存，CS-AML 为 26%，sAML 为 22%，新发 AML 为 54%，P<0.001）。多变量分析。首次完全缓解时的同种异体移植提高了 sAML 和 CS-AML 患者的生存率。总之，这些发现强调了识别 CS-AML 对于改善预后预测和潜在治疗意义的临床意义。 （NILG AML 02/06；临床试验政府标识符：NCT00495287）。
Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently identified by the clinical history or specific morphological and cytogenetic abnormalities. However, in the absence of these features, uncertainties to identify the secondary nature of some cases, otherwise defined as de novo AML, remain. In order to test whether a chromatinspliceosome (CS) mutational signature might better define the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients who were enrolled in a randomized clinical trial (NILG AML 02/06) and who provided samples for accurate cytogenetic and molecular characterization. Among clinically defined de novo AML, 17.6% carried CS mutations (CS-AML) and showed clinical characteristics closer to sAML (older age, lower white blood cell counts and higher rate of multilineage dysplasia). Outcomes in this group were adverse, more similar to those of sAML as compared to de novo AML (overall survival, 30% in CS-AML and 17% in sAML vs. 61% in de novo AML, P<0.0001; disease-free survival, 26% in CS-AML and 22% in sAML vs. 54% of de novo AML, P<0.001) and independently confirmed by multivariable analysis. Allogeneic transplant in first complete remission improved survival in both sAML and CS-AML patients. In conclusion, these findings highlight the clinical significance of identifying CS-AML for improved prognostic prediction and potential therapeutic implications. (NILG AML 02/06; clinicaltrials gov. Identifier: NCT00495287).
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影响因子：
11.4
作者：
通讯作者：
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影响因子：
30.8
作者：
Makishima H;Yoshizato T;Yoshida K;Sekeres MA;Radivoyevitch T;Suzuki H;Przychodzen B;Nagata Y;Meggendorfer M;Sanada M;Okuno Y;Hirsch C;Kuzmanovic T;Sato Y;Sato-Otsubo A;LaFramboise T;Hosono N;Shiraishi Y;Chiba K;Haferlach C;Kern W;Tanaka H;Shiozawa Y;Gómez-Seguí I;Husseinzadeh HD;Thota S;Guinta KM;Dienes B;Nakamaki T;Miyawaki S;Saunthararajah Y;Chiba S;Miyano S;Shih LY;Haferlach T;Ogawa S;Maciejewski JP
通讯作者：
Maciejewski JP
影响因子：
20.3
作者：
Metzeler, Klaus H.;Herold, Tobias;Spiekermann, Karsten
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Spiekermann, Karsten
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20.3
作者：
Lindsley, R. Coleman;Mar, Brenton G.;Ebert, Benjamin L.
通讯作者：
Ebert, Benjamin L.
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20.3
作者：
Papaemmanuil, Elli;Gerstung, Moritz;Campbell, Peter J.
通讯作者：
Campbell, Peter J.