Sethapati Venkata Rakesh, Jabr Ra'ed, Shune Leyla, El Atrouni Wissam, Gonzales Patrick R, Cui Wei, Golem Shivani
University of Kansas Medical Center, Kansas City, KS, USA.
Case Rep Hematol. 2020 Dec 16;2020:8822670. doi: 10.1155/2020/8822670. eCollection 2020.
Acute myeloid leukemia (AML) with inv(16)(p13.1q22) resulting in fusion is associated with a favorable prognosis. The presence of a KIT mutation modifies it to an intermediate prognosis. Additionally, inv(16) can cooperate with other genetic aberrations to further increase cell proliferation. Coexistence of inv(16) and t(9;22) is extremely rare (20 cases). We present a case of a 55-year-old male with elevated white blood cell count. Bone marrow evaluation and flow cytometry analysis were compatible with AML with monocytic features. Cytogenetic studies revealed two-related clones, a minor clone with inv(16) and a major clone with concurrent inv(16) and t(9;22) rearrangements. Fluorescent in situ hybridization studies confirmed these rearrangements. Molecular analysis detected a p190 transcript protein. mutations were negative. The patient was initially treated with standard induction regimen; 7 daily doses of cytarabine from day 1-day 7, 3 daily doses of daunorubicin from day 1-day 3, and 1 dose of Mylotarg (gemtuzumab ozogamicin) on day 1. The detection of t(9;22) led to the addition of daily doses of dasatinib (tyrosine kinase inhibitor) from day 7 onwards. The patient achieved complete remission on day 45. During his treatment course, he acquired disseminated infection. Day 180 bone marrow evaluation revealed florid relapse with 64% blasts. Cytogenetic study showed clonal evolution of the inv(16) clone with no evidence of the t(9;22) subclone. Eventually, bone marrow transplantation was contraindicated, and the patient was transferred to palliative care. Literature review revealed that AML with co-occurrence of and gene rearrangements was involved by only a small number of cases with de novo and therapy-related AML. Most cases were in myeloid blast crisis of chronic myeloid leukemia (CML). Treatment and prognosis among the de novo AML cases varied and majority of them achieved clinical remission. In contrast, these cytogenetic abnormalities in the blast phase of CML had a poor prognosis. As the prognosis and management of AML is dependent upon the underlying genetic characteristics of the neoplasm, it is imperative to include clinical outcome with such rare combinations of genetic alterations.
伴有inv(16)(p13.1q22)导致 融合的急性髓系白血病（AML）预后良好。KIT突变的存在将其预后改变为中等。此外，inv(16)可与其他基因畸变协同作用，进一步增加细胞增殖。inv(16)与t(9;22)共存极为罕见（20例）。我们报告一例55岁男性白细胞计数升高的病例。骨髓评估和流式细胞术分析与具有单核细胞特征的AML相符。细胞遗传学研究发现两个相关克隆，一个小克隆带有inv(16)，一个大克隆同时带有inv(16)和t(9;22)重排。荧光原位杂交研究证实了这些重排。分子分析检测到一个p190 转录蛋白。 突变呈阴性。患者最初接受标准诱导方案治疗；第1天至第7天每天7剂阿糖胞苷，第1天至第3天每天3剂柔红霉素，第1天1剂麦罗塔（吉妥珠单抗奥唑米星）。t(9;22)的检测导致从第7天起加用每天剂量的达沙替尼（酪氨酸激酶抑制剂）。患者在第45天实现完全缓解。在其治疗过程中，他发生了播散性 感染。第180天的骨髓评估显示明显复发，原始细胞占64%。细胞遗传学研究显示inv(16)克隆的克隆进化，未发现t(9;22)亚克隆的证据。最终，骨髓移植被禁忌，患者被转至姑息治疗。文献综述显示，同时存在 和 基因重排的AML仅涉及少数初发和治疗相关AML病例。大多数病例处于慢性髓系白血病（CML）的髓系原始细胞危象。初发AML病例的治疗和预后各不相同，大多数病例实现了临床缓解。相比之下，CML原始细胞期的这些细胞遗传学异常预后较差。由于AML的预后和管理取决于肿瘤的潜在遗传特征，因此必须将临床结果与这种罕见的基因改变组合包括在内。
