Chou W-C, Chen C-Y, Hou H-A, Lin L-I, Tang J-L, Yao M, Tsay W, Ko B-S, Wu S-J, Huang S-Y, Hsu S-C, Chen Y-C, Huang Y-N, Tseng M-H, Huang C-F, Tien H-F
Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
Leukemia. 2009 Jul;23(7):1303-10. doi: 10.1038/leu.2009.25. Epub 2009 Feb 19.
Acute myeloid leukemia (AML) with t(7;11)(p15;p15), which results in a NUP98-HOXA9 fusion, is a distinct entity, but this subtype has not been characterized in detail. In a comprehensive study comparing 11 such patients with another 482 adult patients, we found that those with t(7;11) were younger (P=0.0076) and female (P=0.0111), with almost all having the M2-subtype of AML (P<0.0001). Even when those with low-risk karyotypes were excluded, patients with t(7;11) had poorer overall survival than the other AML group (median 13.5 and 20 months, respectively, P=0.045) and poorer relapse-free survival (median 6 and 12 months, respectively, P=0.003). The NUP98-HOXA9 fusion was strongly associated with KRAS and WT1 mutations (P=0.015 and P=0.0018, respectively). We characterized four varieties of this fusion, among which NUP98 exon 12/HOXA9 exon 1b was present in all 11 patients. We developed a highly sensitive and specific assay to quantify the abundance of leukemic cells, and found that the fusion remained detectable in morphological complete remission, even after allogeneic stem cell transplantation, suggesting that this disease was highly refractory to very intensive treatment. AML with NUP98-HOXA9 fusion therefore appears to have a distinct clinical and biological profile, and should be regarded as a poor prognostic group.
伴有t(7;11)(p15;p15)（导致NUP98 - HOXA9融合）的急性髓系白血病（AML）是一种独特的疾病实体，但该亚型尚未得到详细描述。在一项对11例此类患者与另外482例成年患者进行比较的综合研究中，我们发现t(7;11)患者更年轻（P = 0.0076）且女性居多（P = 0.0111），几乎所有患者都属于AML的M2亚型（P < 0.0001）。即使排除低风险核型患者，t(7;11)患者的总生存期也比其他AML组更差（中位生存期分别为13.5个月和20个月，P = 0.045），无复发生存期也更差（中位生存期分别为6个月和12个月，P = 0.003）。NUP98 - HOXA9融合与KRAS和WT1突变密切相关（分别为P = 0.015和P = 0.0018）。我们鉴定了该融合的四种变体，其中NUP98外显子12/HOXA9外显子1b存在于所有11例患者中。我们开发了一种高度灵敏且特异的检测方法来定量白血病细胞的丰度，发现即使在异基因干细胞移植后，形态学完全缓解时仍可检测到该融合，这表明该疾病对强化治疗具有高度耐药性。因此，伴有NUP98 - HOXA9融合的AML似乎具有独特的临床和生物学特征，应被视为预后不良的一组。
