Department of Clinical and Molecular Medicine, Hematology Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy.
BMC Cancer. 2019 Jan 10;19(1):50. doi: 10.1186/s12885-019-5265-5.
Philadelphia (Ph) chromosome results from the reciprocal translocation t(9;22)(q34.1;q11.2) and is diagnostic for chronic myeloid leukemia (CML). However, this translocation is also found in acute lymphoid leukemia (ALL), as well as in rare cases of acute myeloid leukemias (AML). Most patients with CML harbor either the e13a2 or the e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. Moreover, several atypical BCR-ABL1 transcripts, beside the most common e1a2, e13a2 and e14a2, have been described, mainly in patients with CML. However, ALL and de novo AML may also carry BCR-ABL1 atypical transcripts which will confer a poor prognosis.
A 78-years old male was admitted at our hospital with clinical and laboratory features allowing to make the diagnosis of AML. No evidence of a preceding CML (splenomegaly or basophilia) was found. The karyotype on G-banded metaphases was 46,XY, t(9;22)(q34;q11). While the molecular analysis was ongoing, the patient started treatment based on hydroxyurea followed by 5-aza-2'-deoxycytidine. The molecular biology analysis revealed the simultaneous presence of the common p190 e1a2 and the rare e6a2 isoforms. Because of persistent pancytopenia and presence of blasts, according to the molecular data, he was then switched to tyrosine kinase inhibitors (TKIs) treatment. Nevertheless, after 2 months, the patient was still refractory to second line treatment dying because of a pulmonary infection.
The atypical p190 e6a2 transcript seems to be associated in AML with aggressive disease. TKI therapy alone does not seem to control the disease. Prompt observations on these patients carrying rare BCR-ABL1 transcripts may help to establish optimal treatment approaches on these aggressive BCR-ABL1 phenotypes in different setting of patients.
费城（Ph）染色体是由相互易位 t（9；22）（q34.1；q11.2）引起的，是慢性髓细胞白血病（CML）的诊断标志。然而，这种易位也存在于急性淋巴细胞白血病（ALL）以及罕见的急性髓细胞白血病（AML）中。大多数 CML 患者存在 e13a2 或 e14a2 BCR-ABL 融合产物，而一小部分病例表达 e1a2 或 e19a2 转录本。此外，除了最常见的 e1a2、e13a2 和 e14a2 外，还描述了几种不典型的 BCR-ABL1 转录本，主要见于 CML 患者。然而，ALL 和初发 AML 也可能携带 BCR-ABL1 不典型转录本，这将导致预后不良。
一名 78 岁男性因临床和实验室特征被收入我院，诊断为 AML。未发现先前存在 CML（脾肿大或嗜碱性粒细胞增多）的证据。G 带中期核型为 46,XY，t（9；22）（q34；q11）。在进行分子分析的同时，患者开始接受羟基脲治疗，随后接受 5-氮杂-2'-脱氧胞苷治疗。分子生物学分析显示同时存在常见的 p190 e1a2 和罕见的 e6a2 同工型。由于持续全血细胞减少和存在原始细胞，根据分子数据，他随后切换为酪氨酸激酶抑制剂（TKI）治疗。然而，在 2 个月后，患者仍然对二线治疗无反应，最终死于肺部感染。
不典型的 p190 e6a2 转录本似乎与 AML 中的侵袭性疾病有关。单独使用 TKI 治疗似乎无法控制疾病。对携带罕见 BCR-ABL1 转录本的这些患者进行及时观察，可能有助于在不同患者背景下确定这些侵袭性 BCR-ABL1 表型的最佳治疗方法。
