Hébert J, Cayuela J M, Daniel M T, Berger R, Sigaux F
Laboratoire d'Hématologie Moléculaire, Hôpital Saint-Louis, Paris, France.
Blood. 1994 Oct 1;84(7):2291-6.
Acute myelomonocytic leukemia with bone marrow eosinophilia (AML-M4Eo in the French-American-British FAB] classification) is frequently associated with pericentric inversion of chromosome 16, inv(16)(p13q22). Recently, the molecular cloning of teh breakpoints has led to the identification of the two fused genes, CBFB on 16q and MYH11 on 16p. We have analyzed 24 patients with AML-M4Eo at diagnosis and 47 patients with AML of other FAB subtypes, by a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for the CBFB/MYH11 fusion mRNAs. Three types of fusion mRNAs were detected in 22 samples of AML-M4Eo (type A, n = 20; type C, n = 1; and type D, n = 1). Among these 22 positive samples, inv(16) was found in the 20 cytogenetically studied cases. No fusion transcript was detected in two patients with AML-M4Eo and in patients with other types of AML. These results confirm that CBFB/MYH11 transcripts (with a predominant type A form) are present in most cases of inv(16) AML. Moreover, detection of the hybrid transcript is closely associated with the finding of abnormal bone marrow (BM) eosinophils in AML-M4Eo as it is not found in other, FAB subtypes of AML, including AML-M4. To assess the presence of type A CBFB/MYH11 fusion transcripts in five AML-M4Eo patients in remission, we designed a sensitive assay combining nested PCR and allele-specific amplification (NPASA). Residual leukemia cells were detected in four patients who were in remission from 4 to 22 months, but not in one patient in long-term remission (5 years). The clinical relevance of persistent CBFB/MYH11 fusion transcripts in remission remains to be established by studying a large prospective series of patients. NPASA provides a useful and sensitive tool for the detection of minimal residual disease in inv(16) AML and, potentially, in other leukemias associated with translocations that result in a predominant fusion transcript.
伴有骨髓嗜酸性粒细胞增多的急性粒单核细胞白血病（在法美英FAB分类中为AML-M4Eo）常与16号染色体臂间倒位inv(16)(p13q22)相关。最近，断点的分子克隆已导致鉴定出两个融合基因，16q上的CBFB和16p上的MYH11。我们通过针对CBFB/MYH11融合mRNA的逆转录聚合酶链反应（RT-PCR）分析，对24例诊断为AML-M4Eo的患者和47例其他FAB亚型的AML患者进行了检测。在22份AML-M4Eo样本中检测到三种类型的融合mRNA（A型，n = 20；C型，n = 1；D型，n = 1）。在这22份阳性样本中，20例经细胞遗传学研究的病例中发现了inv(16)。在2例AML-M4Eo患者和其他类型AML患者中未检测到融合转录本。这些结果证实，CBFB/MYH11转录本（以主要的A型形式）存在于大多数inv(16) AML病例中。此外，杂合转录本的检测与AML-M4Eo中异常骨髓嗜酸性粒细胞的发现密切相关，因为在其他FAB亚型的AML中未发现，包括AML-M4。为了评估5例缓解期AML-M4Eo患者中A型CBFB/MYH11融合转录本的存在情况，我们设计了一种结合巢式PCR和等位基因特异性扩增（NPASA）的敏感检测方法。在缓解4至22个月的4例患者中检测到残留白血病细胞，但在长期缓解（5年）的1例患者中未检测到。缓解期持续存在的CBFB/MYH11融合转录本的临床相关性仍有待通过对大量前瞻性患者系列进行研究来确定。NPASA为检测inv(16) AML以及可能在其他与导致主要融合转录本的易位相关的白血病中的微小残留病提供了一种有用且敏感的工具。
