Inokuchi K, Iwakiri R, Futaki M, Hanawa H, Tanosaki S, Nomura T, Dan K
Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Leuk Lymphoma. 1998 May;29(5-6):553-61. doi: 10.3109/10428199809050915.
Here we studied minimal residual disease (MRD) of patients with acute myeloid leukemia (AML) who have PML/RAR alpha or AML1/ETO as well as the phenotypic analysis of lymphocyte subsets involved in antitumor immunity. Eight patients in long-term (LT; 3 to 15 years) and 15 patients in short-term (ST; up to 3 years) remission were studied. Using the reverse transcription-polymerase chain reaction (RT) assay, the limit of detection was 10(-5) to 10(-6) for PML/RAR alpha transcript and 10(-4) to 10(-5) for the AML1/ETO transcript. Simultaneously, T lymphocyte subsets and NK cells from the peripheral blood (PB) and bone marrow (BM) were investigated by flow cytometric analysis. Four of the eight patients in LT and 7 of the 15 patients in ST remission were MRD-positive. Although all MRD-positive patients in LT remission are still until now event-free, 3 of the 7 MRD-positive (MRD+) patients in ST remission soon relapsed. The total populations of CD4+, CD8+ and CD56+ [possible T-cell and natural killer (T/NK) populations] in the BM of ST patients and MRD+/LT patients were significantly (p < .01) low. The CD8+ CD28+ population showed the same tendency (p < .01-.02). The T/NK subsets in the BM of MRD-negative (MRD-) LT (MRD-/LT) patients showed similar numbers of cells as normal volunteers. Basically, the total percentage of the CD4+, CD8+ and CD56+ cell populations in the BM was increased and in the following order: MRD-/LT patients, normal volunteers, MRD+/LT patients and MRD+ or -/ST patients. The percentages of the T/NK-cell subsets in the PB were not significantly different among these groups. Thus, the difference of the possible T/NK-cell phenotype in the BM may strongly influence clinical and molecular remission. These results still remain to be confirmed by further studies of the functional anti-tumor immunity of T/NK cells of AML in remission.
在此，我们研究了患有急性髓系白血病（AML）且具有早幼粒细胞白血病/维甲酸受体α（PML/RARα）或AML1/ETO的患者的微小残留病（MRD），以及参与抗肿瘤免疫的淋巴细胞亚群的表型分析。研究了8例长期（LT；3至15年）缓解和15例短期（ST；至多3年）缓解的患者。使用逆转录-聚合酶链反应（RT）检测法，PML/RARα转录本的检测限为10^(-5)至10^(-6)，AML1/ETO转录本的检测限为10^(-4)至10^(-5)。同时，通过流式细胞术分析研究外周血（PB）和骨髓（BM）中的T淋巴细胞亚群和自然杀伤（NK）细胞。8例LT缓解患者中有4例，15例ST缓解患者中有7例MRD呈阳性。尽管所有LT缓解的MRD阳性患者至今仍无事件发生，但7例ST缓解的MRD阳性（MRD+）患者中有3例很快复发。ST患者和MRD+/LT患者骨髓中CD4+、CD8+和CD56+[可能的T细胞和自然杀伤（T/NK）细胞群体]的总数显著（p <.01）降低。CD8+ CD28+细胞群体表现出相同趋势（p <.01-.02）。MRD阴性（MRD-）LT（MRD-/LT）患者骨髓中的T/NK亚群细胞数量与正常志愿者相似。基本上，骨髓中CD4+、CD8+和CD56+细胞群体的总百分比增加，且顺序如下：MRD-/LT患者、正常志愿者、MRD+/LT患者以及MRD+或-/ST患者。这些组外周血中T/NK细胞亚群的百分比无显著差异。因此，骨髓中可能的T/NK细胞表型差异可能强烈影响临床和分子缓解。这些结果仍有待通过对缓解期AML患者T/NK细胞的功能性抗肿瘤免疫进行进一步研究来证实。
