Monosomal karyotype in acute myeloid leukemia:: A better indicator of poor prognosis than a complex karyotype
Monosomal karyotype in acute myeloid leukemia:: A better indicator of poor prognosis than a complex karyotype
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DOI：
10.1200/jco.2008.16.0259
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发表时间：
2008-10-10
影响因子：
45.3
通讯作者：
Lowenberg, Bob
中科院分区：
文献类型：
--
作者：
Breems, Dimitri A.;Van Putten, Wim L. J.;Lowenberg, Bob
目的 探讨复杂核型的各种细胞遗传学成分在急性髓系白血病 (AML) 中的预后价值。患者和方法 对 1,975 名 15 至 60 岁的 AML 患者进行细胞遗传学和总生存 (OS) 分析。结果 除了细胞遗传学（CN）正常和核心结合因子（CBF）异常的 AML 之外，我们还区分了 733 名细胞遗传学异常的患者。在后一个亚组中，单个染色体的丢失 (n = 109) 会带来负面的预后影响（4 年 OS，12%；结果不佳）。 7 号染色体缺失最为常见，但具有单一单体-7 的 AML 患者（n = 63；4 年 OS，13%）和其他单一常染色体单体（n = 46；4 年 OS，12%）的结果没有差异。结构性染色体异常影响预后仅与单一常染色体单体有关（4 年 OS，极差者为 4%，差者为 24%）。我们得出了单体核型（MK）作为 AML 预后极差的预测因子，该核型指的是两个或多个不同的常染色体单体（n = 116；4 年 OS，3%）或存在结构异常的单个常染色体单体（n = 68；4 年 OS，4%）。在直接比较中，MK 提供了比传统定义的复杂核型（考虑任何三个或更多或五个或更多克隆细胞遗传学异常）更好的预后预测，也比与非常差的结果相关的各种个体特异性细胞遗传学异常（例如 del[5q]、inv[3]/t[3;3]）提供更好的预后预测。结论 MK（除了 CN 和 CBF 之外）能够对细胞遗传学异常 AML 的两种新聚集进行预后分类，即不利风险 MK 阴性类别（4 年 OS，26% +/- 2%）和高度不利风险 MK 阳性类别（4 年 OS，4% +/- %）。
Purpose To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML). Patients and Methods Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years. Results Besides AML with normal cytogenetics (CN) and core binding factor (CBF) abnormalities, we distinguished 733 patients with cytogenetic abnormalities. Among the latter subgroup, loss of a single chromosome (n = 109) conferred negative prognostic impact (4-year OS, 12%; poor outcome). Loss of chromosome 7 was most common, but outcome of AML patients with single monosomy -7 (n = 63; 4- year OS, 13%) and other single autosomal monosomies (n = 46; 4-year OS, 12%) did not differ. Structural chromosomal abnormalities influenced prognosis only in association with a single autosomal monosomy (4-year OS, 4% for very poor v 24% for poor). We derived a monosomal karyotype (MK) as a predictor for very poor prognosis of AML that refers to two or more distinct autosomal chromosome monosomies (n = 116; 4-year OS, 3%) or one single autosomal monosomy in the presence of structural abnormalities (n = 68; 4-year OS, 4%). In direct comparisons, MK provides significantly better prognostic prediction than the traditionally defined complex karyotype, which considers any three or more or five or more clonal cytogenetic abnormalities, and also than various individual specific cytogenetic abnormalities (eg, del[5q], inv[3]/t[3; 3]) associated with very poor outcome. Conclusion MK enables (in addition to CN and CBF) the prognostic classification of two new aggregates of cytogenetically abnormal AML, the unfavorable risk MK-negative category (4-year OS, 26% +/- 2%) and the highly unfavorable risk MK-positive category (4- year OS, 4% +/- %).