目的:混合表型急性白血病(MPAL)是一种罕见的血液系统恶性肿瘤,其中白血病细胞不能被分配到任何特定的谱系。缺乏明确的定义,与病理相关的诊断标准使MPAL患者的临床处理具有挑战性。我们在此报告了两名小儿MPAL患者骨髓细胞的遗传发现。
方法:使用G显带检查骨髓细胞,阵列比较基因组杂交,RNA测序,逆转录聚合酶链反应,桑格测序,和荧光原位杂交。
结果:在第一个病人中,遗传分析揭示了染色体带8p11,10p11,11q21和17p11,嵌合体MLLT10::PICALM和PICALM::MLLT10的结构畸变,以及染色体2,4,8,13和21上的不平衡(增加/损失).在21q中还发现了亚显微缺失,包括RUNX1基因座。第二个病人,染色体带1p32、8p11、12p13、20p13和20q11,嵌合体ETV6::LEXM和NCOA6::ETV6的结构畸变,染色体2、8、11、12、16、19、X,和Y。
结论:来自两名MPAL患者的白血病细胞携带染色体畸变,导致融合基因以及基因组失衡,导致许多基因位点的得失。检测到的融合基因可能代表了主要的白血病事件,尽管得失也可能在白血病发生中起作用。
OBJECTIVE: Mixed phenotype acute leukemia (MPAL) is a rare hematologic malignancy in which the leukemic cells cannot be assigned to any specific lineage. The lack of well-defined, pathogenetically relevant diagnostic criteria makes the clinical handling of MPAL patients challenging. We herein report the genetic findings in bone marrow cells from two pediatric MPAL patients.
METHODS: Bone marrow cells were examined using G-banding, array comparative genomic hybridization, RNA sequencing, reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in situ hybridization.
RESULTS: In the first patient, the genetic analyses revealed structural aberrations of chromosomal bands 8p11, 10p11, 11q21, and 17p11, the chimeras MLLT10::
PICALM and
PICALM::MLLT10, and imbalances (gains/losses) on chromosomes 2, 4, 8, 13, and 21. A submicroscopic deletion in 21q was also found including the RUNX1 locus. In the second patient, there were structural aberrations of chromosome bands 1p32, 8p11, 12p13, 20p13, and 20q11, the chimeras ETV6::LEXM and NCOA6::ETV6, and imbalances on chromosomes 2, 8, 11, 12, 16, 19, X, and Y.
CONCLUSIONS: The leukemic cells from both MPAL patients carried chromosome aberrations resulting in fusion genes as well as genomic imbalances resulting in gain and losses of many gene loci. The detected fusion genes probably represent the main leukemogenic events, although the gains and losses are also likely to play a role in leukemogenesis.