Departments of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Laboratory Medicine, Zhongshan Hospital Fudan University, Shanghai, China.
Departments of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Leuk Res. 2021 Jul;106:106584. doi: 10.1016/j.leukres.2021.106584. Epub 2021 Apr 24.
While dysregulation of MYC has been implicated in acute myeloid leukemia (AML), the impact of MYC protein expression in AML is less well understood. We investigated the correlation of MYC protein expression by immunohistochemistry (MYC-IHC) with MYC abnormalities and prognosis in adult de novo AML. MYC-IHC in bone marrow of patients with untreated AML (n = 58) was assessed and scored as MYC (0-40 % of blasts) or MYC (> 40 % of blasts). This was correlated with MYC abnormalities by fluorescence in situ hybridization (FISH) and prognosis in the context of cytogenetic risk stratification. Residual myeloid disease at the end of induction was assessed by flow cytometry. MYC and MYC were detected in 24 (41 %) and 34 cases (59 %), respectively. Extra copies of MYC were present in 12 % of cases and were not correlated with level of MYC-IHC. No cases had MYC translocation or amplification. Compared to MYC patients, MYC patients had a shorter overall survival in all cytogenetic risk groups (68 vs. 21 months, p = 0.006) and in the intermediate risk group (61 vs. 21 months, p = 0.046). MYC patients had a tendency towards detected residual disease at the end of induction in all cytogenetic risk and intermediate risk groups. Regardless of the underlying mechanisms of MYC dysregulation, high level of MYC protein is expressed in the majority of AML and correlated to worse prognosis. Further studies on MYC dysregulation in leukemogenesis and therapy targeting MYC aberration are warranted.
虽然 MYC 的失调已被认为与急性髓系白血病（AML）有关，但 MYC 蛋白表达在 AML 中的影响尚不清楚。我们研究了免疫组织化学（MYC-IHC）检测的 MYC 蛋白表达与成人初发 AML 中的 MYC 异常和预后的相关性。对未经治疗的 AML 患者（n = 58）的骨髓进行 MYC-IHC 评估，并按 MYC（blasts 的 0-40%）或 MYC（blasts 的>40%）进行评分。通过荧光原位杂交（FISH）检测 MYC 异常，并在细胞遗传学风险分层的背景下评估与预后的相关性。通过流式细胞术评估诱导结束时残留的髓系疾病。在 24 例（41%）和 34 例（59%）病例中分别检测到 MYC 和 MYC。在 12%的病例中存在 MYC 额外拷贝，但与 MYC-IHC 水平无关。没有病例存在 MYC 易位或扩增。与 MYC 患者相比，在所有细胞遗传学风险组（68 与 21 个月，p = 0.006）和中间风险组（61 与 21 个月，p = 0.046）中，MYC 患者的总生存期均更短。在所有细胞遗传学风险组和中间风险组中，MYC 患者在诱导结束时均有残留疾病的趋势。无论 MYC 失调的潜在机制如何，大多数 AML 中均表达高水平的 MYC 蛋白，并与预后更差相关。有必要进一步研究 MYC 失调在白血病发生中的作用以及针对 MYC 异常的治疗靶点。
