Late appearance of eosinophilia in myeloid blast phase of myeloid neoplasm with rearrangement of PDGFRβ
Late appearance of eosinophilia in myeloid blast phase of myeloid neoplasm with rearrangement of PDGFRβ
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伴有 PDGFRβ 重排的髓系肿瘤的髓系母细胞期晚期出现嗜酸性粒细胞增多
DOI：
10.1080/10428194.2020.1731499
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发表时间：
2020
影响因子：
2.6
通讯作者：
Ohashi K
中科院分区：
文献类型：
--
作者：
Nagata A;Doki N;Harada H;Takezaki T;Konishi T;Yamada Y;Kaito S;Kurosawa S;Yoshifuji K;Harada K;Sakaguchi M;Yasuda S;Yoshioka K;Watakabe-Inamoto K;Toya T;Igarashi A;Najima Y;Muto H;Kobayashi T;Kakihana K;Harada Y;Sakamaki H;Ohashi K
血小板衍生生长因子受体（PDGFRb）基因位于染色体5q31 - 33;其重排导致组成型酪氨酸激酶活性[1]。在WHO分类中，与PDGFRb基因融合相关的血液恶性肿瘤被归类为伴嗜酸性粒细胞增多和PDGFRb重排的髓样/淋巴样肿瘤[2]。在大多数情况下，PDGFRb重排的髓样/淋巴样肿瘤表现为骨髓增殖性肿瘤（MPN）、骨髓增生异常综合征（MDS）/MPN重叠肿瘤（慢性粒单核细胞白血病、非典型慢性粒细胞白血病、青少年粒单核细胞白血病）、MDS、急性髓性白血病（AML）、急性淋巴细胞白血病（ALL）等[1，3]。与伴有PDGFRa重排的髓样/淋巴样肿瘤不同，嗜酸性粒细胞增多症不是诊断髓样/淋巴样肿瘤和PDGFRb重排所必需的[1 - 3]，有时难以诊断。据报道，酪氨酸激酶抑制剂（TKI）在该疾病的慢性期产生长期反应[4]。然而，由于急变期的病例很少，因此没有关于这种恶性肿瘤急变期标准治疗的报道。在这里，我们报告了一个独特的情况下，急变期骨髓/淋巴肿瘤和PDGFRb重排的诊断基础上存在显着的嗜酸性粒细胞增多化疗后，并没有响应TKI的权利，从一开始。一名有威尔逊病史的56岁妇女接受了定期体检，实验室数据正常。一个月后，患者转诊接受白细胞增多症评价。入院时的实验室检查显示白细胞增多伴白血病原始细胞和血小板减少，白色血细胞（WBC）计数为86.2 × 103/ll（原始细胞28.5%，淋巴细胞11.0%，中性粒细胞40.5%，单核细胞14.0%，嗜酸性粒细胞6.0%），血小板计数为6.9 × 104/ll。骨髓（BM）穿刺物（图1（a））显示骨髓细胞过多，过氧化物酶阳性成髓细胞占27.7%，免疫表型如下：分化簇（CD）CD13：84.5%，CD 33：95.7%，CD 11b：35.9%，CD 14：1.2%。BM的其他代表性组分为8.9%嗜酸性粒细胞、8.2%单核细胞、2.0%淋巴细胞、47.7%髓系（除成髓细胞外）和4.8%红系。她的血红蛋白水平为8.6 g/dl。骨髓穿刺液的常规细胞遗传学分析显示46，XX，add（5）（q31），add（7）（q11）。2），d12，der（？）t（？; 7）（？;问题11. 2)在20个中期细胞中有15个。患者被诊断为未另行说明的成熟型AML，接受了诱导治疗，包括艾达鲁肽和阿糖胞苷（AraC），患者未达到血液学完全缓解，诱导治疗后出现了显著的嗜酸性粒细胞增多。诱导治疗后41天获得的全血细胞计数显示血红蛋白为11.0 g/dl，WBC计数为13.9 103/ll，血小板计数为3.6 104/ll。分类计数显示循环单核细胞中嗜酸性粒细胞占17.0%，中性粒细胞占44.0%，淋巴细胞占12.5%，单核细胞占20.5%。此时BM涂片显示骨髓细胞增多，成熟嗜酸性粒细胞占60.4%，成髓细胞占7.8%（图1（B））。此外，此时BM细胞的光谱核型荧光原位杂交（FISH）分析显示46，XX，t（5; 12）（q33; p13），t（7; 12）（q11. 2; q24. 1)在20个中期分裂相中的15个中期分裂相（图1（c））中，PDGFRb的FISH分析在81.0%的外周血细胞中分裂信号呈阳性。因此，患者被诊断为骨髓性肿瘤，
Platelet-derived growth factor receptor (PDGFRb) gene is located on chromosome 5q31-33; its rearrangement leads to constitutive tyrosine kinase activity [1]. Hematological malignancies associated with PDGFRb gene fusions are classified as myeloid/lymphoid neoplasm with eosinophilia and rearrangement of PDGFRb in WHO classification [2]. In most cases, myeloid/lymphoid neoplasm with rearrangement of PDGFRb presents phenotypically as myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS)/MPN overlap neoplasm (chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, juvenile myelomonocytic leukemia), MDS, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and so on [1, 3]. As distinct from myeloid/lymphoid neoplasm with rearrangement of PDGFRa, eosinophilia is not necessary for the diagnosis of myeloid/lymphoid neoplasm and rearrangement of PDGFRb [1-3], and it is sometimes difficult to diagnose. Tyrosine kinase inhibitors (TKIs) reportedly produce a long-term response in the chronic phase of this disease [4]. However, there are no reports about standard therapies in the blast phase of this malignancy because of the rarity of cases in the blast phase. Here, we report a unique case of blast phase myeloid/lymphoid neoplasm and rearrangement of PDGFRb that was diagnosed based on the presence of significant eosinophilia after chemotherapy, and that did not respond to TKIs right from the outset. A 56-year-old woman with a history of WilsonLs disease got a regular medical checkup, and laboratory data was normal. One month later, the patient was referred for the evaluation of leukocytosis. Laboratory studies on admission revealed leukocytosis with leukemic blasts and thrombocytopenia, with a white blood cell (WBC) count of 86.2 Â103/ll (28.5% blast cells, 11.0% lymphocytes, 40.5% neutrophils, 14.0% monocytes, and 6.0% eosinophils) and platelet count of 6.9 Â104/ll. A bone marrow (BM) aspirate (Figure 1 (a)) showed hypercellular marrow with 27.7% peroxidase-positive myeloblasts with the following immunophenotype: cluster of differentiation (CD) À13: 84.5%, CD33: 95.7%, CD11b: 35.9%, and CD14: 1.2%. Other representative components of BM were 8.9% eosinophils, 8.2% monocytes, 2.0% lymphocytes, 47.7% myeloid series except myeloblasts, and 4.8% erythroid series. Her hemoglobin level was 8.6 g/dl. Conventional cytogenetic analyses of the BM aspirate revealed 46, XX, add (5)(q31), add (7)(q11. 2), À12, der (?) t (?; 7)(?; q11. 2) in 15 out of 20 metaphases. The patient was diagnosed with AML with maturation, not otherwise specified and received induction therapy, including idarubicin and cytarabine (AraC).The patient did not achieve hematological complete remission, and developed significant eosinophilia after the induction therapy. Complete blood count obtained 41days after the induction therapy showed a hemoglobin of 11.0 g/dl, WBC count of 13.9 Â 103/ll, and platelet count of 3.6 Â104/ll. A differential count revealed 17.0% eosinophils, 44.0% neutrophils, 12.5% lymphocytes, and 20.5% monocytes among the circulating mononuclear cells. BM smear at this time showed hyper cellular marrow with 60.4% of mature eosinophils and 7.8% of myeloblasts (Figure 1 (b)). Moreover, spectral karyotyping fluorescence in situ hybridization (FISH) analysis of BM cells at this time revealed 46, XX, t (5; 12)(q33; p13), t (7; 12)(q11. 2; q24. 1) in 15 out of 20 metaphases (Figure 1 (c)) and FISH analysis for PDGFRb was positive for a split signal in 81.0% of the peripheral blood cells. Therefore, the patient was diagnosed as myeloid neoplasm with
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影响因子：
11.4
作者：
通讯作者：
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影响因子：
20.3
作者：
Makishima, Hideki;Jankowska, Anna M.;Maciejewski, Jaroslaw P.
通讯作者：
Maciejewski, Jaroslaw P.
影响因子：
3.1
作者：
Arefi, Maryam;Garcia, Juan L.;Hernandez-Rivas, Jesus M.
通讯作者：
Hernandez-Rivas, Jesus M.
血小板衍生生长因子受体β相关急性髓性白血病患者对甲磺酸伊马替尼有显着反应
影响因子：
2.1
作者：
Y. Shimomura;H. Maruoka;T. Ishikawa
通讯作者：
T. Ishikawa
影响因子：
4.8
作者：
Böhmer, FD;Karagyozov, L;Dove, S
通讯作者：
Dove, S