HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.
HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.
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DOI：
10.1182/blood.v84.1.244.bloodjournal841244
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发表时间：
1994-07
期刊：
影响因子：
20.3
通讯作者：
A. Scott;David;Head;K. Kopecky;Frederick;Appelbaum;K. Theil;Michael;Grever;I. Chen;Michael H. Whittaker;B. Griffith;J. Licht;S. Waxman;M. Whalen;A. Bankhurst;L. Richter;T. Grogan;Cheryl L. Willrnan
中科院分区：
文献类型：
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作者：
A. Scott;David;Head;K. Kopecky;Frederick;Appelbaum;K. Theil;Michael;Grever;I. Chen;Michael H. Whittaker;B. Griffith;J. Licht;S. Waxman;M. Whalen;A. Bankhurst;L. Richter;T. Grogan;Cheryl L. Willrnan
我们已经确定并表征了一种以前未被识别的急性白血病形式，它具有髓系细胞和自然杀伤(NK)细胞的特征。从连续350例成人初治急性髓系白血病(AML)中，我们鉴定出20例(6%)具有独特的免疫表型：CD33+、CD56+、CD11a+、CD13lo、CD15lo、CD34+/-、HLA-DR-、CD16-。多色流式细胞仪检测证实髓系(CD33、CD13、CD15)和NK细胞相关抗原(CD56)共表达，逆转录聚合酶链式反应(RT-PCR)检测证实CD56(神经细胞黏附分子)在白血病细胞中表达。虽然有2例表达了CD4，但无1例表达CD2、CD3或CD8，也没有1例显示T细胞受体(TCRβ、γ、Delta)基因的克隆性重排。大多数白血病细胞具有与急性早幼粒细胞白血病(APL)相似的独特形态特征(核膜深度内陷，胞浆稀少，嗜天青颗粒细小，苏丹红B和髓过氧化物酶细胞化学反应细小)，特别是小颗粒变异体(FAB AML-M3v)。20例均缺失t(15；17)，RT-PCR检测17例缺失早幼粒细胞/维甲酸受体α(RARα)融合转录本，12例核型为46，XX或46，XY，2例染色体17q：1伴有del(17)(Q25)，1例t(11；17)(q23；q21)及早幼粒细胞白血病锌指/RARα融合转录本。所有被检测的病例(6/20)，包括t(11；17)的病例，在体外对全反式维甲酸(ATRA)的反应未能分化，这表明这些病例可能解释了一些对ATRA没有临床反应的APL。6例受试者中有4例表现出功能性NK细胞介导的细胞毒作用，提示这些独特的CD33+、CD56+、CD16-急性白血病与正常CD56+、CD16-NK前体细胞有关。结合平移和多参数流式细胞仪分选，我们在健康人的外周血中发现了正常的CD56+、CD33+、CD16-对应细胞，频率为1%到2%。我们的研究表明，这种形式的急性白血病可能源于髓系和NK细胞谱系共同的前体细胞的转化，因此我们建议将其命名为髓系/NK急性白血病。对这一新的白血病实体的认识将是区分这些ATRA无反应性病例和ATRA反应性真正的APL的重要因素。
We have identified and characterized a previously unrecognized form of acute leukemia that shares features of both myeloid and natural killer (NK) cells. From a consecutive series of 350 cases of adult de novo acute myeloid leukemia (AML), we identified 20 cases (6%) with a unique immunophenotype: CD33+, CD56+, CD11a+, CD13lo, CD15lo, CD34+/-, HLA-DR-, CD16-. Multicolor flow cytometric assays confirmed the coexpression of myeloid (CD33, CD13, CD15) and NK cell-associated (CD56) antigens in each case, whereas reverse transcription polymerase chain reaction (RT-PCR) assays confirmed the identity of CD56 (neural cell adhesion molecule) in leukemic blasts. Although two cases expressed CD4, no case expressed CD2, CD3, or CD8 and no case showed clonal rearrangement of genes encoding the T-cell receptor (TCR beta, gamma, delta). Leukemic blasts in the majority of cases shared unique morphologic features (deeply invaginated nuclear membranes, scant cytoplasm with fine azurophilic granularity, and finely granular Sudan black B and myeloperoxidase cytochemical reactivity) that were remarkably similar to those of acute promyelocytic leukemia (APL); particularly the microgranular variant (FAB AML-M3v). However, all 20 cases lacked the t(15;17) and 17 cases tested lacked the promyelocytic/retinoic acid receptor alpha (RAR alpha) fusion transcript in RT-PCR assays; 12 cases had 46,XX or 46,XY karyotypes, whereas 2 cases had abnormalities of chromosome 17q: 1 with del(17)(q25) and the other with t(11;17)(q23;q21) and the promyelocytic leukemia zinc finger/RAR alpha fusion transcript. All cases tested (6/20), including the case with t(11;17), failed to differentiate in vitro in response to all-trans retinoic acid (ATRA), suggesting that these cases may account for some APLs that have not shown a clinical response to ATRA. Four of 6 cases tested showed functional NK cell-mediated cytotoxicity, suggesting a relationship between these unique CD33+, CD56+, CD16- acute leukemias and normal CD56+, CD16- NK precursor cells. Using a combination of panning and multiparameter flow cytometric sorting, we identified a normal CD56+, CD33+, CD16- counterpart cell at a frequency of 1% to 2% in the peripheral blood of healthy individuals. Our studies suggest that this form of acute leukemia may arise from transformation of a precursor cell common to both the myeloid and NK cell lineages; thus we propose the designation myeloid/NK acute leukemia. Recognition of this new leukemic entity will be important in distinguishing these ATRA-nonresponsive cases from ATRA-responsive true APL.