Cimino G, Rapanotti M C, Elia L, Biondi A, Fizzotti M, Testi A M, Tosti S, Croce C M, Canaani E, Mandelli F
Dipartimento di Biopatologia Umana, University La Sapienza, Rome, Italy.
Cancer Res. 1995 Apr 15;55(8):1625-8.
We have analyzed by Southern blotting the ALL-1 (MLL, HRX, Hrtx 1) gene configuration in a series of 126 patients with acute myeloid leukemia (AML) representative of all ages and French-American-British Classification groups and correlated this genetic feature with clinical and biological features at diagnosis. ALL-1 gene rearrangements were detected in 17 of the 74 cases with M4-M5 (myelomonocytic and monocytic) AML and in 2 of the 52 cases with other leukemic subtypes (P < 0.01). Within the series of 74 M4-M5 patients, ALL-1 rearrangements were significantly associated with French-American-British Classification M5 (P = 0.009), high WBC (P = 0.002), and young age. In particular, all 5 infant (< 1.5 years) AML cases, 6 of the 19 (31%) patients between 1.5 and 18 years of age, and 6 of the 50 (12%) patients > 18 years old showed an altered ALL-1 genomic configuration (P < 0.001). Immunophenotypic characterization revealed coexpression of lymphoid and myeloid markers in 6 of 17 ALL-1 rearranged M4-M5 cases. The IgH gene configuration was studied in 77 of 126 AMLs. Five patients (6%) showed IgH clonal rearrangements and all were in the ALL-1 rearranged group (P < 0.0001). Our findings indicate that ALL-1 rearrangement is the commonest genetic alteration presently detectable in M4-M5 AML, particularly in childhood where it is found in up to one-third of all cases. The association of IgH rearrangements with ALL-1 alterations in AML, coupled to the frequent detection in this subset of lymphoid associated markers, further supports the origin of these tumors from a common multipotent precursor with bipotential lymphoid and monocytic differentiation capability.
我们通过Southern印迹法分析了126例急性髓细胞白血病（AML）患者的ALL-1（MLL、HRX、Hrtx 1）基因结构，这些患者代表了所有年龄以及法国-美国-英国协作组分类的各个组，并将这一基因特征与诊断时的临床和生物学特征进行了关联分析。在74例M4-M5（粒单核细胞和单核细胞）AML患者中，有17例检测到ALL-1基因重排，在52例其他白血病亚型患者中有2例检测到ALL-1基因重排（P<0.01）。在74例M4-M5患者系列中，ALL-1重排与法国-美国-英国协作组分类的M5（P = 0.009）、高白细胞计数（P = 0.002）以及年轻年龄显著相关。特别地，所有5例婴儿（<1.5岁）AML病例、19例1.5至18岁患者中的6例（31%）以及50例>18岁患者中的6例（12%）均显示ALL-1基因组结构改变（P<0.001）。免疫表型特征分析显示，17例ALL-1重排的M4-M5病例中有6例同时表达淋巴样和髓样标志物。在126例AML患者中的77例研究了IgH基因结构。5例患者（6%）显示IgH克隆性重排，且均在ALL-1重排组中（P<0.0001）。我们的研究结果表明，ALL-1重排是目前在M4-M5 AML中可检测到的最常见的基因改变，尤其是在儿童期，高达三分之一的病例中可发现这种改变。AML中IgH重排与ALL-1改变的关联，以及在这一亚组中频繁检测到淋巴样相关标志物，进一步支持了这些肿瘤起源于具有双潜能淋巴样和单核细胞分化能力的共同多能前体细胞。
