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Abstract：
BACKGROUND: Myelodysplastic syndrome (MDS) is caused by malignant proliferation and ineffective hematopoiesis. Oncogenic somatic mutations and increased apoptosis, necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells. An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage. Bone marrow cellularity and myeloblasts usually increase with disease progression. However, aplastic crisis occasionally occurs in advanced MDS.
METHODS: A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1 (MDS-EB-1) based on an increase in the percentages of myeloblasts and cluster of differentiation (CD)34+ hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples. The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years. In the treatment process, the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia. During the aplastic crisis, the bone marrow was infiltrated with sparsely distributed atypical lymphocytes. Surprisingly, the leukemic cells disappeared. Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3, CD5, CD8, CD16, CD56 and CD57, suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer (NK)/NKT cells that suppressed both normal and leukemic hematopoiesis. Elevated serum levels of inflammatory cytokines, including interleukin (IL)-6, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), confirmed the deranged type I immune responses. This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia. Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche. Antituberculosis treatment led to reversion of the aplastic crisis, disappearance of the atypical lymphocytes, increased marrow cellularity and 2 mo of hematological remission, providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis, the regression of leukemic cells and the activation of CD56+ atypical lymphocytes. Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state. However, the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.
CONCLUSIONS: Disseminated tuberculosis can induce CD56+ lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis, resulting in the development of aplastic crisis and leukemic cell regression.
METHODS: A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1 (MDS-EB-1) based on an increase in the percentages of myeloblasts and cluster of differentiation (CD)34+ hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples. The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years. In the treatment process, the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia. During the aplastic crisis, the bone marrow was infiltrated with sparsely distributed atypical lymphocytes. Surprisingly, the leukemic cells disappeared. Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3, CD5, CD8, CD16, CD56 and CD57, suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer (NK)/NKT cells that suppressed both normal and leukemic hematopoiesis. Elevated serum levels of inflammatory cytokines, including interleukin (IL)-6, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), confirmed the deranged type I immune responses. This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia. Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche. Antituberculosis treatment led to reversion of the aplastic crisis, disappearance of the atypical lymphocytes, increased marrow cellularity and 2 mo of hematological remission, providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis, the regression of leukemic cells and the activation of CD56+ atypical lymphocytes. Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state. However, the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.
CONCLUSIONS: Disseminated tuberculosis can induce CD56+ lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis, resulting in the development of aplastic crisis and leukemic cell regression.
摘要：
背景：骨髓增生异常综合征（MDS）是由恶性增生和无效造血引起的。致癌体细胞突变和凋亡增加，坏死和焦亡导致早期造血祖细胞的积累和成熟血细胞的生产力受损。成髓细胞百分比的增加和不利的体细胞突变的存在是白血病造血的迹象和进入晚期的指标。骨髓细胞和成髓细胞通常随疾病进展而增加。然而,再生危机偶尔发生在先进的MDS。
方法：根据骨髓样本中成髓细胞和分化簇（CD）34+造血祖细胞百分比的增加以及骨髓肿瘤相关体细胞突变的鉴定，一名72岁男性患者被明确诊断为有过量母细胞-1（MDS-EB-1）的MDS。患者接受低甲基化治疗，并能够保持稳定的疾病状态2年。在治疗过程中,晚期MDS患者出现了进行性全血细胞减少和骨髓发育不全.在再生危机期间，骨髓浸润有稀疏分布的非典型淋巴细胞。令人惊讶的是,白血病细胞消失了.免疫学分析显示，非典型淋巴细胞表达CD3，CD5，CD8，CD16，CD56和CD57的频率很高，表明自身免疫细胞毒性T淋巴细胞和自然杀伤（NK）/NKT细胞的激活抑制了正常和白血病造血。血清炎性细胞因子水平升高，包括白细胞介素（IL）-6，干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α），证实了紊乱的I型免疫反应。这种形态学和免疫学特征导致诊断为继发于大颗粒淋巴细胞白血病的严重再生障碍性贫血。放射学检查怀疑播散性结核病，以寻找炎性利基。抗结核治疗导致再生危机的逆转，非典型淋巴细胞的消失，骨髓细胞性增加和2个月的血液学缓解，提供强有力的证据表明，传播的结核病是导致再障危机发展的原因，白血病细胞的消退和CD56+非典型淋巴细胞的激活。在接下来的19个月内恢复低甲基化治疗使患者保持稳定的疾病状态。然而,患者将疾病表型转化为急性髓细胞性白血病,最终死于疾病进展和严重感染.
结论：播散性结核可诱导骨髓中CD56+淋巴细胞浸润，进而抑制正常和白血病的造血，导致再生障碍性危机和白血病细胞消退的发展。
方法：根据骨髓样本中成髓细胞和分化簇（CD）34+造血祖细胞百分比的增加以及骨髓肿瘤相关体细胞突变的鉴定，一名72岁男性患者被明确诊断为有过量母细胞-1（MDS-EB-1）的MDS。患者接受低甲基化治疗，并能够保持稳定的疾病状态2年。在治疗过程中,晚期MDS患者出现了进行性全血细胞减少和骨髓发育不全.在再生危机期间，骨髓浸润有稀疏分布的非典型淋巴细胞。令人惊讶的是,白血病细胞消失了.免疫学分析显示，非典型淋巴细胞表达CD3，CD5，CD8，CD16，CD56和CD57的频率很高，表明自身免疫细胞毒性T淋巴细胞和自然杀伤（NK）/NKT细胞的激活抑制了正常和白血病造血。血清炎性细胞因子水平升高，包括白细胞介素（IL）-6，干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α），证实了紊乱的I型免疫反应。这种形态学和免疫学特征导致诊断为继发于大颗粒淋巴细胞白血病的严重再生障碍性贫血。放射学检查怀疑播散性结核病，以寻找炎性利基。抗结核治疗导致再生危机的逆转，非典型淋巴细胞的消失，骨髓细胞性增加和2个月的血液学缓解，提供强有力的证据表明，传播的结核病是导致再障危机发展的原因，白血病细胞的消退和CD56+非典型淋巴细胞的激活。在接下来的19个月内恢复低甲基化治疗使患者保持稳定的疾病状态。然而,患者将疾病表型转化为急性髓细胞性白血病,最终死于疾病进展和严重感染.
结论：播散性结核可诱导骨髓中CD56+淋巴细胞浸润，进而抑制正常和白血病的造血，导致再生障碍性危机和白血病细胞消退的发展。
