Raghavachar A, Bartram C R, Gaedicke G, Binder T, Heil G, Carbonell F, Kubanek B, Kleihauer E
Leuk Res. 1986;10(11):1293-9. doi: 10.1016/0145-2126(86)90336-x.
The cellular origin of acute undifferentiated leukemia (AUL) is still a matter of controversy. We report on two cases in which the diagnosis of AUL was established according to restricted criteria. Blast cells of both patients showed phenotypic conversion during the course of disease. In one case, within 24 days from starting treatment, the leukemic phenotype changed from AUL to acute myelomonocytic leukemia (FAB L1, TdT+ to FAB M4, TdT-). The initial phenotype of this acute leukemia was characterized by the co-expression of both B-lymphoid and myeloid markers on the same cell. Moreover, analysis of esterase isoenzyme pattern showed the whole spectrum of isoenzymes typically seen in myelomonocytic leukemias already at diagnosis, yet blast cells additionally contained all three isoenzymes of beta-hexosaminidase typically seen in AUL. However, examination of immunoglobulin (Ig) heavy chain gene rearrangement initially and after conversion revealed an identical monoclonal configuration of Ig heavy chain sequences in both samples. The second AUL patient relapsed after allogeneic bone marrow transplantation with common ALL-antigen (CALLA) positive acute leukemia. Subsequent Southern blot analysis showed a novel rearranged Ig fragment compared to the analysis before transplantation indicating that the leukemic clones prior to and after transplantation were not identical. No chromosomal abnormalities were observed in both cases. These data support the view that AUL cells originate from a pluripotent stem cell that is capable to differentiate in the myelomonocytic lineage (patient 1), and confirm the value of Ig gene analysis as marker for cellular clonality.
急性未分化白血病（AUL）的细胞起源仍是一个有争议的问题。我们报告了两例根据严格标准确诊为AUL的病例。两名患者的原始细胞在病程中均出现表型转换。在一例中，从开始治疗起24天内，白血病表型从AUL转变为急性粒单核细胞白血病（FAB L1，TdT+转变为FAB M4，TdT-）。这种急性白血病的初始表型特征是同一细胞上同时表达B淋巴细胞和髓系标志物。此外，酯酶同工酶谱分析显示，在诊断时已经出现了粒单核细胞白血病中常见的全谱同工酶，但原始细胞还额外含有AUL中常见的β-己糖胺酶的所有三种同工酶。然而，对免疫球蛋白（Ig）重链基因重排的初始检测以及转换后的检测显示，两个样本中Ig重链序列具有相同的单克隆构型。第二例AUL患者在异基因骨髓移植后复发，复发时为普通ALL抗原（CALLA）阳性的急性白血病。随后的Southern印迹分析显示，与移植前的分析相比，出现了一个新的重排Ig片段，表明移植前后的白血病克隆并不相同。两例均未观察到染色体异常。这些数据支持以下观点：AUL细胞起源于能够向粒单核细胞系分化的多能干细胞（患者1），并证实了Ig基因分析作为细胞克隆性标志物的价值。
