Semchenkova Alexandra, Mikhailova Ekaterina, Komkov Alexander, Gaskova Marina, Abasov Ruslan, Matveev Evgenii, Kazanov Marat, Mamedov Ilgar, Shmitko Anna, Belova Vera, Miroshnichenkova Anna, Illarionova Olga, Olshanskaya Yulia, Tsaur Grigory, Verzhbitskaya Tatiana, Ponomareva Natalia, Bronin Gleb, Kondratchik Konstantin, Fechina Larisa, Diakonova Yulia, Vavilova Liudmila, Myakova Natalia, Novichkova Galina, Maschan Alexey, Maschan Michael, Zerkalenkova Elena, Popov Alexander
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117998 Moscow, Russia.
Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117998 Moscow, Russia.
Int J Mol Sci. 2022 Apr 5;23(7):4019. doi: 10.3390/ijms23074019.
We report incidence and deep molecular characteristics of lineage switch in 182 pediatric patients affected by B-cell precursor acute lymphoblastic leukemia (BCP-ALL), who were treated with blinatumomab. We documented six cases of lineage switch that occurred after or during blinatumomab exposure. Therefore, lineage conversion was found in 17.4% of all resistance cases (4/27) and 3.2% of relapses (2/63). Half of patients switched completely from BCP-ALL to CD19-negative acute myeloid leukemia, others retained CD19-positive B-blasts and acquired an additional CD19-negative blast population: myeloid or unclassifiable. Five patients had gene rearrangements; one had translocation. The presented cases showed consistency of gene rearrangements and fusion transcripts across initially diagnosed leukemia and lineage switch. In two of six patients, the clonal architecture assessed by gene rearrangements was stable, while in others, loss of clones or gain of new clones was noted. -r patients demonstrated very few additional mutations, while in the case, lineage switch was accompanied by a large set of additional mutations. The immunophenotype of an existing leukemia sometimes changes via different mechanisms and with different additional molecular changes. Careful investigation of all BM compartments together with all molecular -minimal residual disease studies can lead to reliable identification of lineage switch.
我们报告了182例接受blinatumomab治疗的B细胞前体急性淋巴细胞白血病（BCP-ALL）儿科患者中谱系转换的发生率和深度分子特征。我们记录了6例在blinatumomab暴露后或期间发生的谱系转换病例。因此，在所有耐药病例（4/27）的17.4%和复发病例（2/63）的3.2%中发现了谱系转换。一半的患者从BCP-ALL完全转换为CD19阴性急性髓系白血病，其他患者保留CD19阳性B原始细胞并获得额外的CD19阴性原始细胞群体：髓系或无法分类。5例患者有基因重排；1例有易位。所呈现的病例显示了最初诊断的白血病和谱系转换之间基因重排和融合转录本的一致性。在6例患者中的2例中，通过基因重排评估的克隆结构是稳定的，而在其他患者中，观察到克隆丢失或新克隆的获得。-r患者显示出很少的额外突变，而在该病例中，谱系转换伴随着大量额外突变。现有白血病的免疫表型有时通过不同机制并伴随不同的额外分子变化而改变。对所有骨髓区室以及所有分子微小残留病研究进行仔细调查可导致谱系转换的可靠识别。
