Varella-Garcia M, Hogan C J, Odom L F, Murata-Collins J L, Ai H, Chen L, Richkind K, Paskulin G, Andreeff M, Brizard A, McGavran L, Gemmill R M, Berger R, Drabkin H A
Division of Medical Oncology, University of Colorado Health Sciences and Cancer Centers, Denver 80262, USA.
Leukemia. 2001 Sep;15(9):1408-14. doi: 10.1038/sj.leu.2402219.
Many patients with t(8;21) AML have residual positive cells during remission. We previously developed D-FISH probes that detect both derivative chromosomes and the normal alleles. In negative controls, only 2/44,000 (0.0045%) positive signals were observed. To investigate MRD, we examined specimens from 29 patients who had initially obtained CR. In remission patients, 61% had 1-4/2000 positive cells (0.05-0.19%). Higher frequencies were found in two patients in early relapse and in one patient in early remission. However, a negative test did not exclude relapse. Since false positives were negligible and because most t(8;21) AMLs express CD34, we asked whether cell sorting combined with FISH would increase the sensitivity. In one patient, we observed that 80% of CD34+ cells were t(8;21)+ at 2 months from initial clinical and cytogenetic remission. However, by 5 months the pre- and post-sorted populations contained 0.15% and 0.06% t(8;21) cells, respectively. Whereas essentially all t(8;21) cells in the initial specimen expressed CD34, only 0.6% were subsequently CD34+. These results are consistent with in vitro assays showing that residual t(8;21) cells undergo differentiation. Thus, FISH can identify MRD in a majority of t(8;21) patients and, combined with CD34+ selection, may provide an indirect assessment of the differentiation state of residual t(8;21) cells.
许多t(8;21)急性髓系白血病（AML）患者在缓解期仍有残留的阳性细胞。我们之前开发了能同时检测衍生染色体和正常等位基因的双色荧光原位杂交（D-FISH）探针。在阴性对照中，仅观察到2/44,000（0.0045%）个阳性信号。为了研究微小残留病（MRD），我们检测了29例最初获得完全缓解（CR）患者的标本。在缓解期患者中，61%有1 - 4/2000个阳性细胞（0.05 - 0.19%）。在2例早期复发患者和1例早期缓解患者中发现了更高的频率。然而，检测结果为阴性并不能排除复发。由于假阳性可忽略不计，且大多数t(8;21) AML表达CD34，我们探讨了细胞分选结合FISH是否会提高敏感性。在1例患者中，我们观察到从初始临床和细胞遗传学缓解起2个月时，80%的CD34+细胞为t(8;21)+。然而，到5个月时，分选前后的细胞群体中t(8;21)细胞分别占0.15%和0.06%。尽管初始标本中基本上所有t(8;21)细胞都表达CD34，但随后只有0.6%的细胞为CD34+。这些结果与体外试验一致，表明残留的t(8;21)细胞会发生分化。因此，FISH可在大多数t(8;21)患者中识别MRD，并且与CD34+选择相结合，可能会间接评估残留t(8;21)细胞的分化状态。
