Lo Coco F, Mandelli F, Breccia M, Annino L, Guglielmi C, Petti M C, Testi A M, Alimena G, Croce C M, Canaani E
Department of Human Biopathology, University La Sapienza, Rome, Italy.
Cancer Res. 1993 Aug 15;53(16):3800-3.
The chromosome 11q23 band is a genetic region frequently involved in nonrandom karyotypic abnormalities of acute leukemia. A genomic locus named ALL-1 or MLL, where 11q23 breakpoints are clustered, has been recently cloned and characterized. We have made use of an ALL-1-specific probe in Southern blot experiments to analyze the configuration of this gene in a large series of acute leukemia patients, representative of all different myeloid and lymphoid subtypes. Nine of 145 cases (6.2%) showed abnormal ALL-1 restriction fragments in leukemic DNAs. Of these nine cases, five patients in whom karyotypic data were available displayed chromosome 11q23 aberrations, including t(4;11) (three cases) and t(9;11) (two cases). Immunophenotypic and morphocytochemical characterization of ALL-1-rearranged acute leukemia revealed prevalence of poorly differentiated B lymphoid and/or monoblastic features. Considering the whole series, ALL-1 rearrangements were significantly associated with female sex, higher white blood cell counts at presentation, and very poor clinical outcome. The presence of residual disease was molecularly documented in one case at the time of clinical remission after induction treatment and was followed by early relapse. We conclude that ALL-1 rearrangements are new molecular markers of human leukemia with considerable diagnostic and prognostic relevance.
11号染色体q23带是急性白血病非随机核型异常中经常涉及的一个遗传区域。一个名为ALL-1或MLL的基因组位点最近已被克隆和鉴定，11q23断点在该位点聚集。我们利用ALL-1特异性探针进行Southern印迹实验，分析了一大系列急性白血病患者（代表所有不同的髓系和淋巴系亚型）中该基因的结构。145例患者中有9例（6.2%）白血病DNA显示ALL-1限制性片段异常。在这9例患者中，5例有核型数据的患者显示11号染色体q23畸变，包括t(4;11)（3例）和t(9;11)（2例）。ALL-1重排的急性白血病的免疫表型和形态细胞化学特征显示，低分化B淋巴细胞和/或单核母细胞特征占优势。考虑整个系列，ALL-1重排与女性、初诊时较高的白细胞计数以及非常差的临床结局显著相关。在1例患者诱导治疗临床缓解时分子学证实存在残留疾病，随后早期复发。我们得出结论，ALL-1重排是人类白血病新的分子标志物，具有相当大的诊断和预后意义。
