The immunophenotype of minimally differentiated acute myeloid leukemia (AML-M0):: reduced immunogenicity and high frequency of CD34+/CD38- leukemic progenitors
The immunophenotype of minimally differentiated acute myeloid leukemia (AML-M0):: reduced immunogenicity and high frequency of CD34+/CD38- leukemic progenitors
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DOI：
10.1038/sj.leu.2401519
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发表时间：
1999-10-01
期刊：
影响因子：
11.4
通讯作者：
Olive, D
中科院分区：
文献类型：
--
作者：
Costello, RT;Mallet, F;Olive, D
最小分化急性髓细胞白血病（AML-M0）是一种罕见的FAB亚型（占AML的2-3%），预后不良。我们的研究目的是表征AML-MO表达和参与免疫识别的粘附/共刺激分子的调节，测试体外原始细胞的免疫原性，并确定白血病祖细胞的百分比。在这里，我们证明了在初级混合淋巴细胞反应中，AML-NIO的同种免疫识别，如通过响应T细胞的IL-2分泌所评估的，与更分化的亚型相比减少（128 +/- 95 pg/ml vs 304 +/- 159 pg/ml，P < 0.05）。这些数据与主要组织相容性复合体（MHC）II类DR分子和CD 28配体B7-2（在AML免疫识别中起重要作用）的原始细胞低表达一致。粘附/共刺激分子上调白血病细胞刺激通过CD 40，虽然效率较低，γ-干扰素，这两种刺激改善母细胞免疫原性。我们还证明，与分化程度更高的AML（2.5% +/-2）或非白血病CD 34（+）造血前体（1.8% +/-0.8）相比，AML-M0具有非常高的CD 34（+）/CD 38（-）白血病克隆前体百分比（40% +/-30）。由于早期分化阶段白血病细胞群的存在已被确定为不良预后因素，我们得出结论，AML-M0中CD 34（+）/CD 38（-）原始细胞的高频率可能与已经确定的不良预后因素如化疗耐药和细胞遗传学异常相一致。AML-M0体外免疫原性受损和CD 34（+）/CD 38（-）原始细胞百分比高的临床意义需要对其他患者进行比较分析。CD 40触发后母细胞的免疫原性增加为AML-M0免疫治疗提供了有趣的线索，这必须用小鼠体内白血病模型来证实。
Minimally differentiated acute myeloid leukemia (AML-M0) is a rare FAB subtype (2-3% of AMLs) of poor prognosis. The aim of our study was to characterize AML-MO expression and regulation of adhesion/costimulatory molecule involved in immune recognition, to test blast in vitro immunogenicity, and to determine the percentage of leukemia progenitor cells. Here, we demonstrate that alloimmune recognition of AML-NIO in primary mixed lymphocyte reaction, as evaluated by IL-2 secretion of responding T cells, is reduced in comparison with more differentiated subtypes (128 +/- 95 pg/ml vs 304 +/- 159 pg/ml, P < 0.05). These data are in line with low blast cell expression of major histocompatibility complex (MHC) class II DR molecules, and of the CD28 ligand B7-2, which plays an important role in AML immune recognition. Adhesion/costimulatory molecules were up-regulated by leukemic cell stimulation via CD40, and, although less efficiently, by gamma-IFN; both stimuli improved blast cell immunogenicity. We also demonstrate that AML-M0 have a very high percentage (40% +/- 30) of CD34(+)/CD38(-) leukemic clonogenic precursors in comparison with more differentiated AMLs (2.5% +/- 2) or non-leukemic CD34(+) hematopoietic precursors (1.8% +/- 0.8). Since the presence of a leukemic cell population at an early differentiation stage has been identified as a poor prognostic factor, we conclude that the high frequency of CD34(+)/CD38(-) blasts in AML-M0 may converge with already identified poor prognosis factors such as chemotherapy resistance and cytogenetic abnormalities. The clinical implications of AML-M0 impaired in vitro immunogenicity and a high percentage of CD34(+)/CD38(-) blasts will require comparative analysis of additional patients. The increased immunogenicity of blast cells after CD40 triggering provide interesting clues for AML-M0 immunotherapy, that have to be confirmed with an in vivo leukemia model in mice.