Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically
Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically
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DOI：
10.1038/s41375-019-0390-3
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发表时间：
2019-07-01
期刊：
影响因子：
11.4
通讯作者：
Bloomfield, Clara D.
中科院分区：
文献类型：
--
作者：
Mrozek, Krzysztof;Eisfeld, Ann-Kathrin;Bloomfield, Clara D.
在10-12%的急性髓性白血病（AML）患者中检测到具有>= 3个异常的复杂核型（CK），并且与不良预后相关。在CK中发现的最常见的不平衡异常导致来自5 q、7 q和/或17 p染色体臂的物质的损失。5 q、7 q和/或17 p异常的存在表示典型的CK，它们的缺失表示非典型的CK。由于CK-AML的分子特征尚未得到很好的表征，我们研究了160例临床特征良好的患者中81个白血病/癌症相关基因的突变状态。其中136例患者有≥ 3个完全不平衡染色体异常，其中96例有典型CK，40例有非典型CK，24例患者有≥ 1个平衡异常和≥ 2个不平衡异常。典型CK-AML患者与典型CK-AML患者不同：他们携带TP 53突变的频率较低（P < 0.001），而携带PHF 6（P = 0.008）、FLT 3-TKD（P = 0.02）、MED 12（P = 0.02）和NPM 1（P = 0.02）突变的频率较高。非典型和典型CK-AML患者年龄小（P = 0.007），WBC（P = 0.001）、骨髓（P < 0.001）和血液（P = 0.006）原始细胞百分比高，完全缓解率高（P = 0.02），总生存期长（P < 0.001），表明非典型和典型CK-AML构成不同的疾病亚型。我们还在典型和非典型CK-AML中确定了较小的患者亚群，这些亚群在分子和临床上不同。
Complex karyotype (CK) with >= 3 abnormalities is detected in 10-12% of patients with acute myeloid leukemia (AML) and associated with poor prognosis. The most common unbalanced abnormalities found in CK result in loss of material from the 5q, 7q, and/or 17p chromosome arms. The presence of 5q, 7q, and/or 17p abnormalities denotes typical CK and their absence denotes atypical CK. Since molecular features of CK-AML are not well characterized, we investigated mutational status of 81 leukemia/cancer-associated genes in 160 clinically well-characterized patients. They included 136 patients with >= 3 exclusively unbalanced chromosome abnormalities, 96 of whom had a typical CK and 40 atypical CK, and 24 patients with >= 1 balanced abnormality in addition to >= 2 unbalanced ones. Patients with a typical CK-AML differed from those with typical CK-AML: they carried TP53 mutations less often (P < 0.001) and more often PHF6 (P = 0.008), FLT3-TKD (P = 0.02), MED12 (P = 0.02), and NPM1 (P = 0.02) mutations. They were younger (P = 0.007), had higher WBC (P = 0.001) and percentages of marrow (P < 0.001) and blood (P = 0.006) blasts, higher complete remission rates (P = 0.02), and longer overall survival (P < 0.001), thus indicating that atypical and typical CK-AMLs constitute distinct disease subtypes. We also identified smaller patient subsets within both typical and atypical CK-AML that differed molecularly and clinically.