Poirel H, Radford-Weiss I, Rack K, Troussard X, Veil A, Valensi F, Picard F, Guesnu M, Leboeuf D, Melle J
Department of Hematology, CHU Necker-Enfants Malades, Paris, France.
Blood. 1995 Mar 1;85(5):1313-22.
Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult. Characterization of the two genes involved in the inv(16)(p13q22), CBF beta and MYH11, has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction (RT-PCR). We have analyzed CBF beta-MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias, with or without eosinophilia, to determine whether their presence correlates with morphology. Fifty-three cases (11 AML M4Eo; 1 AML M4 with atypical abnormal eosinophils (AML M4 "Eo"); 29 AML M4; 8 AML M5; 3 CMML; and 1 AML M2 with eosinophilia) were analyzed. All 11 typical AML M4Eo were CBF beta-MYH11 positive. The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype, RT-PCR and fluorescent in situ hybridization (FISH). Three of 29 (10%) AML M4 without abnormal eosinophils were CBF beta-MYH11 positive, 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis (2 not tested). Both cases tested also showed MYH11 genomic rearrangement. None of the other leukemias were RT-PCR positive. Follow-up of three patient showed residual positivity in apparent complete remission. These data show that CBF beta-MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo, but also in approximately 10% of AML M4 without eosinophilic abnormalities, a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest. Taken together with the detection of CBF beta-MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques, these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4, regardless of morphologic features, to allow accurate evaluation of the prognostic importance of this fusion transcript.
对经典上与急性髓系白血病M4Eo相关的16号染色体异常进行核型检测可能具有挑战性。对inv(16)(p13q22)所涉及的两个基因CBFβ和MYH11进行特征分析，使得通过逆转录聚合酶链反应（RT-PCR）检测融合转录本成为可能。我们通过RT-PCR分析了伴有或不伴有嗜酸性粒细胞增多的骨髓单核细胞白血病中的CBFβ-MYH11融合转录本，以确定它们的存在是否与形态学相关。分析了53例病例（11例急性髓系白血病M4Eo；1例伴有非典型异常嗜酸性粒细胞的急性髓系白血病M4（急性髓系白血病M4“Eo”）；29例急性髓系白血病M4；8例急性髓系白血病M5；3例慢性粒-单核细胞白血病；以及1例伴有嗜酸性粒细胞增多的急性髓系白血病M2）。所有11例典型的急性髓系白血病M4Eo均为CBFβ-MYH11阳性。1例伴有独特嗜酸性粒细胞异常的急性髓系白血病M4病例，其核型、RT-PCR和荧光原位杂交（FISH）检测均为阴性。29例无异常嗜酸性粒细胞的急性髓系白血病M4中有3例（10%）为CBFβ-MYH11阳性，其中1例通过经典中期分析未显示任何明显的16号染色体异常（2例未检测）。所检测的2例病例也显示有MYH11基因重排。其他白血病均无RT-PCR阳性。对3例患者的随访显示，在明显完全缓解期仍有残留阳性。这些数据表明，CBFβ-MYH11融合转录本不仅存在于绝大多数典型的急性髓系白血病M4Eo中，也存在于约10%无嗜酸性粒细胞异常的急性髓系白血病M4中，这一发生率远高于急性髓系白血病M4中16号染色体异常的零星报道。结合在经典显带技术未显示明显16号染色体异常的情况下检测到CBFβ-MYH11转录本，这些数据表明，所有急性髓系白血病M4，无论形态学特征如何，均应通过RT-PCR或FISH进行额外筛查，以便准确评估这种融合转录本的预后重要性。
