Aguiar R C, Chase A, Coulthard S, Macdonald D H, Carapeti M, Reiter A, Sohal J, Lennard A, Goldman J M, Cross N C
Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, MA, USA.
Blood. 1997 Oct 15;90(8):3130-5.
Two distinct leukemia syndromes are associated with abnormalities of chromosome band 8p11. First, a myeloproliferative disorder with features characteristic of both chronic myeloid leukemia and non-Hodgkin's lymphoma and second, an acute myeloid leukemia (AML) with French-American-British (FAB) M4/5 morphology and prominent erythrophagocytosis. The two syndromes are exemplified by a t(8;13)(p11;q12) and a t(8;16)(p11;p13), respectively, but cytogenetic variants of both have been described. Recently, the t(8;16) has been cloned and shown to fuse the MOZ gene at 8p11 to the CBP gene at 16p13. We have used fluorescence in situ hybridization (FISH), Southern blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) to refine the 8p11 breakpoint in three cases with t(8;13)(p11;q12) and in a single case of AML-M5 with a clinical picture apparently identical to that found in patients with a t(8;16), but characterized by an inv(8)(p11q13). FISH analysis was performed with several 8p11 CEPH yeast artificial chromosome (YAC) clones. YAC 782H11 was centromeric to the one case with t(8;13) tested, but was telomeric to the inv(8). YAC 847B12 was telomeric to both the t(8;13) and the inv(8), whereas YAC 829D12 was centromeric to the t(8;13), but split by the inv(8). Southern blotting and PCR of YAC 829D12 showed that it contained the MOZ gene. A 900-bp MOZ fragment encompassing the published t(8;16) breakpoint was amplified by PCR from normal peripheral blood leukocyte cDNA and used to probe Southern blots of patient DNA. A rearrangement was detected in the case with inv(8), but not in any of the three cases with t(8;13). Southern blotting with a CBP probe and RT-PCR with MOZ and CBP primers suggested that the inv(8) does not result in a cryptic MOZ-CBP fusion. It is likely, therefore, that MOZ is fused to a novel gene at 8q13 in this case. We conclude that the t(8;13) breakpoint is flanked by YACs 782H11 and 847B12 and is at least 1 Mb telomeric to MOZ. MOZ is involved, however, in a new variant of the t(8;16).
两种不同的白血病综合征与染色体8p11带的异常相关。第一种是具有慢性髓性白血病和非霍奇金淋巴瘤特征的骨髓增殖性疾病，第二种是具有法美英（FAB）M4/5形态且有显著红细胞吞噬作用的急性髓性白血病（AML）。这两种综合征分别以t(8;13)(p11;q12)和t(8;16)(p11;p13)为代表，但两者的细胞遗传学变异均有报道。最近，t(8;16)已被克隆，并显示8p11处的MOZ基因与16p13处的CBP基因融合。我们使用荧光原位杂交（FISH）、Southern印迹法和逆转录聚合酶链反应（RT-PCR）来精确确定3例t(8;13)(p11;q12)患者以及1例AML-M5患者8p11处的断点，该AML-M5患者的临床表现与t(8;16)患者明显相同，但特征为inv(8)(p11q13)。使用几个8p11 CEPH酵母人工染色体（YAC）克隆进行FISH分析。YAC 782H11在检测的1例t(8;13)患者中位于着丝粒侧，但在inv(8)患者中位于端粒侧。YAC 847B12在t(8;13)和inv(8)患者中均位于端粒侧，而YAC 829D12在t(8;13)患者中位于着丝粒侧，但被inv(8)分开。对YAC 829D12进行Southern印迹法和PCR分析表明它包含MOZ基因。通过PCR从正常外周血白细胞cDNA中扩增出一个包含已发表的t(8;16)断点的900 bp MOZ片段，并用于探测患者DNA的Southern印迹。在inv(8)患者中检测到重排，但在3例t(8;13)患者中均未检测到。用CBP探针进行Southern印迹法以及用MOZ和CBP引物进行RT-PCR分析表明inv(8)不会导致隐匿性MOZ-CBP融合。因此，在这种情况下，MOZ可能与8q13处的一个新基因融合。我们得出结论，t(8;13)断点位于YAC 782H11和847B12两侧，且至少在MOZ端粒侧1 Mb处。然而，MOZ参与了t(8;16)的一种新变异。
