Yan Ling-Zhi, Chen Su-Ning, Ping Na-Na, Wang Qin-Rong, Liu Hong, Ding Zi-Xuan, Zhu Ming-Qing, Liang Jian-Ying, Liu Dan-Dan, Cen Jian-Nong, Pan Jin-Lan, Qiu Hui-Ying, Sun Ai-Ning, Wu De-Pei
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou 215006, Jiangsu Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Oct;21(5):1116-20. doi: 10.7534/j.issn.1009-2137.2013.05.006.
The purpose of this study was to summary the clinical and laboratorial features in 15 adult cases of mixed phenotypic acute leukemia with Ph chromosome and/or BCR-ABL fusion gene positive (Ph(+)MPAL), 15 adult patients with Ph(+)MPAL were defined by WHO-2008 classification. The clinical characteristics, results of morphology, immunology, cytogenetics and molecular genetic detections and results of follow-up in 15 adult patients with Ph(+)MPAL were analyzed retrospectively. The results showed that 15 patients among 87 cases of MPAL demonstrated Ph(+)MPAL (17.2%; 15/87) (7 males and 8 females), their median age was 51 (range 16-81) year old and median WBC count at diagnosis was 69 (12.7-921)×10(9)/L. Based on FAB criteria, these patients showed different morphologic types, including AML (13.3%; 2/15), ALL (40.0%; 6/15), HAL (46.7%; 7/15). Immunologic analysis indicated that 15 cases of Ph(-)MPAL were all classified as B-lymphoid +myeloid mixed immunophenotype. Except one patient, all expressed CD34 antigen on the surface of leukemia cells with 64.3% strong positive, only Ph (53.3%; 8/15), Ph with additional chromosomal abnormalities (33.3%; 5/15) and normal karyotype (13.3%; 2/15) were cytogenetically identified. BCR-ABL fusion gene transcript positive were detected by multiplex reverse transcription PCR in all cases, with e1a2 subtype (p190) (40.0%; 6/15) and b2a2 or b3a2 (p210) subtype (60.0%; 9/15). Four out of 7 (57.1%) patients were found to have IKZF1 gene deletion, without other common gene mutations. Seven out of 10 cases (70.0%) achieved complete remission (CR) after one cycle of induction chemotherapy. In the induction stage, CR rate seemed higher when tyrosine kinase inhibitors (TKI) were added to chemotherapy (83.3%:50.0%; P = 0.206). Overall survival (OS) in 4 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was longer than that in 4 patients received chemotherapy alone (P = 0.004). It is concluded that Ph(+)MPAL mainly is expressed as B+My phenotype. The majority of patients is older and has CD34 overexpression. In the aspect of molecular genetics, the Ph(+)MPAL is similar to other acute leukemia with Ph chromosome. Ph(+)MPAL is a subtype of acute leukemia with poor prognosis. WBC count at diagnosis is an independent prognostic factor. The combination of TKI and allo-HSCT can improve their long-term survival, which needs to be confirmed through carrying out a prospective and multicenter clinical trial for newly diagnosed Ph(+)MPAL.
本研究旨在总结15例伴有Ph染色体和/或BCR-ABL融合基因阳性（Ph(+)MPAL）的成年混合表型急性白血病患者的临床和实验室特征，15例成年Ph(+)MPAL患者依据WHO-2008分类标准确诊。对15例成年Ph(+)MPAL患者的临床特征、形态学、免疫学、细胞遗传学及分子遗传学检测结果和随访结果进行回顾性分析。结果显示，87例MPAL患者中有15例表现为Ph(+)MPAL（17.2%；15/87）（男7例，女8例），中位年龄51岁（范围16 - 81岁），诊断时中位白细胞计数为69（12.7 - 921）×10⁹/L。根据FAB标准，这些患者表现出不同的形态学类型，包括急性髓系白血病（AML，13.3%；2/15）、急性淋巴细胞白血病（ALL，40.0%；6/15）、混合表型急性白血病（HAL，46.7%；7/15）。免疫分析表明，15例Ph(+)MPAL均被分类为B淋巴细胞+髓系混合免疫表型。除1例患者外，所有患者白血病细胞表面均表达CD34抗原，其中64.3%为强阳性，细胞遗传学鉴定仅发现Ph（53.3%；8/15）、伴有额外染色体异常的Ph（33.3%；5/15）和正常核型（13.3%；2/15）。所有病例通过多重逆转录PCR检测到BCR-ABL融合基因转录本阳性，其中e1a2亚型（p190）（40.0%；6/15）和b2a2或b3a2（p210）亚型（60.0%；9/15）。7例患者中有4例（57.1%）发现IKZF1基因缺失，无其他常见基因突变。10例患者中有7例（70.0%）在1个周期诱导化疗后达到完全缓解（CR）。在诱导期，化疗中加用酪氨酸激酶抑制剂（TKI）时CR率似乎更高（83.3%∶50.0%；P = 0.206）。4例接受异基因造血干细胞移植（allo-HSCT）患者的总生存期（OS）长于4例单纯接受化疗患者（P = 0.004）。结论：Ph(+)MPAL主要表现为B+My表型。大多数患者年龄较大且CD34过表达。在分子遗传学方面，Ph(+)MPAL与其他伴有Ph染色体的急性白血病相似。Ph(+)MPAL是一种预后较差的急性白血病亚型。诊断时白细胞计数是独立的预后因素。TKI与allo-HSCT联合应用可改善其长期生存，这需要通过对新诊断的Ph(+)MPAL开展前瞻性多中心临床试验来证实。
