inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)-ALK fusion gene in myeloid leukemia that developed in an elderly woman
inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)-ALK fusion gene in myeloid leukemia that developed in an elderly woman
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DOI：
10.1007/s12185-013-1482-x
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发表时间：
2014-02-01
影响因子：
2.1
通讯作者：
Ohno, Hitoshi
中科院分区：
文献类型：
--
作者：
Maesako, Yoshitomo;Izumi, Kiyotaka;Ohno, Hitoshi
一位75岁的女性表现为明显的白细胞增多；白细胞计数为143.6 × 10(3)/ μ L，其中38.6%为单核细胞，13.6%为未成熟粒细胞，包括原细胞。骨髓（BM）抽吸涂片显示bbb90 %细胞增生，骨髓系细胞增生，14.6%单核细胞增生，32.1%母细胞增生。粒细胞系列显示一系列发育不良的形态。过氧化物酶阳性率为51.5%。CD36+细胞单核分化占64.6%。从BM中获得的中期切片显示非整倍体核型，具有-7和来自染色体2的亚散心标记染色体，通过Vysis ALK探针的荧光原位杂交确定为inv(2)（p23q13）。逆转录酶介导的聚合酶链反应和核苷酸测序证实了RANBP2 -ALK融合mRNA。骨髓活检标本的高灵敏度抗alk免疫组化显示白血病细胞的核膜染色。由于白血病表现出慢性髓单细胞白血病的特征，患者接受标准的柔红霉素-阿糖胞苷治疗后再加阿扎胞苷治疗，白血病进展得到持久抑制。这些发现表明，inv(2)(p23q13)/RABBP2-ALK定义了髓系白血病的一个小亚群，其特征是分化为单核细胞，并具有骨髓增生异常综合征/骨髓增生性肿瘤的特征。
A 75-year-old woman presented with marked leukocytosis; the white cell count was 143.6 x 10(3)/mu L with 38.6 % monocytes and 13.6 % immature granulocytes, including blasts. Bone marrow (BM) aspirate smears showed > 90 % cellularity with hyperplasia of myeloid-lineage cells, 14.6 % monocytes, and 32.1 % blasts. The granulocyte series showed a range of dysplastic morphologies. The rate of peroxidase positivity was 51.5 %. CD36+ cells with monocytic differentiation comprised 64.6 % mononuclear cells. Metaphase spreads obtained from the BM revealed an aneuploid karyotype with -7 and a submetacentric marker chromosome derived from chromosome 2, which was determined to be inv(2)(p23q13) by fluorescence in situ hybridization using the Vysis ALK probe. RAN-binding protein 2 (RANBP2)-ALK fusion mRNA was confirmed by reverse transcriptase-mediated polymerase chain reaction and nucleotide sequencing. High-sensitivity anti-ALK immunohistochemistry of a BM biopsy specimen demonstrated nuclear membrane staining of leukemia cells. As the leukemia showed features of chronic myelomonocytic leukemia, the patient was treated with standard daunorubicin-cytarabine followed by azacitidine, leading to the durable suppression of leukemia progression. These findings suggest that inv(2)(p23q13)/RABBP2-ALK defines a small subset of myeloid leukemia characterized by differentiation to monocytes and sharing features of myelodysplastic syndrome/myeloproliferative neoplasm.