Wasserman R, Felix C A, McKenzie S E, Shane S, Lange B, Finger L R
Division of Oncology, Children's Hospital of Philadelphia, PA 19104.
Leukemia. 1993 Aug;7(8):1294-9.
In B-precursor acute lymphoblastic leukemia (ALL), the nucleotide sequence of the complementarity determining region III (CDRIII) in the rearranged immunoglobulin heavy chain gene (IgH) has been used as a molecular fingerprint to identify the leukemic cells. In a child with B-precursor ALL without central nervous system (CNS) disease at diagnosis and a subsequent isolated CNS relapse, we examined the stability of the rearranged IgH by comparing the nucleotide sequences of the CDRIII in the leukemic cells from the marrow at diagnosis to the sequences in the leukemic cells from the cerebrospinal fluid at relapse. Whereas two of the three IgH sequences isolated from the leukemic cells at CNS relapse were identical to sequences originally isolated from the marrow lymphoblasts at diagnosis, the third CNS sequence was similar but not identical to the third marrow sequence. The third IgH sequence identified in the CNS differed from the marrow sequence only at the variable gene segment adjoining the CDRIII. Using a detection method based on the polymerase chain reaction, the altered IgH sequence identified in the leukemic cells from the cerebrospinal fluid was noted to be present in the CNS at a higher frequency than the related diagnostic sequence and was not detected in the marrow either at diagnosis or at CNS relapse. These findings indicate that the clonal pattern of leukemia in the CNS may differ from that in the marrow.
在B前体急性淋巴细胞白血病（ALL）中，重排的免疫球蛋白重链基因（IgH）互补决定区III（CDRIII）的核苷酸序列已被用作识别白血病细胞的分子指纹。在一名诊断时无中枢神经系统（CNS）疾病且随后出现孤立性CNS复发的B前体ALL患儿中，我们通过比较诊断时骨髓白血病细胞中CDRIII的核苷酸序列与复发时脑脊液白血病细胞中的序列，来检测重排IgH的稳定性。虽然在CNS复发时从白血病细胞中分离出的三个IgH序列中有两个与诊断时最初从骨髓淋巴母细胞中分离出的序列相同，但第三个CNS序列与第三个骨髓序列相似但不完全相同。在CNS中鉴定出的第三个IgH序列与骨髓序列仅在与CDRIII相邻的可变基因片段处不同。使用基于聚合酶链反应的检测方法，发现脑脊液白血病细胞中鉴定出的改变的IgH序列在CNS中的出现频率高于相关的诊断序列，且在诊断时或CNS复发时的骨髓中均未检测到。这些发现表明，CNS中白血病的克隆模式可能与骨髓中的不同。
