Institute for Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
Int J Lab Hematol. 2021 Jun;43(3):433-440. doi: 10.1111/ijlh.13405. Epub 2020 Nov 26.
Acute myeloid leukemia with normal karyotype (AML-NK) is the largest group of AML patients with very heterogeneous disease outcome. In order to ensure more precise risk stratification new molecular markers have been introduced, like expression level for BAALC (Brain and Acute Leukemia, Cytoplasmic) and MN1 (Meningioma 1) genes.
In this study, we investigated expression level of both genes in 111 adult AML-NK at diagnosis and examined their prognostic potential.
BAALC and MN1 expression were detected in about one third of the patients, and positive correlation between these two genes was found. The BAALC /or MN1 status was not associated with the presence of FLT3-ITD mutations, but exhibited strong correlation with NPM1 status (P < .001). Therefore, among BAALC /or MN1 patients the most frequent ones were FLT3-ITD /NPM1 double negative patients with intermediate prognosis. When BAALC /or MN1 patients were divided into BAALC /BAALC (21/21) and MN1 /MN1 (21/22) groups, we detected that BAALC /or MN1 patients had a tendency toward lower complete remission rate. Also, survival analysis showed that BAALC /or MN1 patients had shorter disease-free survival and overall survival (OS). The most pronounced influence on prognosis was detected in FLT3-ITD /NPM1 group of patients that are lacking reliable prognostic markers, where OS in BAALC /or MN1 was only 5 months vs 25 months in BAALC /or MN1 .
These findings indicate that BAALC and MN1 expression level could be used for more precise risk stratification of AML-NK patients and especially FLT3-ITD /NPM1 patients, transforming this intermediate-risk group, into a group with an adverse prognosis.
具有正常核型的急性髓系白血病（AML-NK）是 AML 患者中最大的一组，其疾病结局存在很大差异。为了确保更精确的风险分层，已经引入了新的分子标志物，如 BAALC（脑和急性白血病，细胞质）和 MN1（脑膜瘤 1）基因的表达水平。
在这项研究中，我们在 111 例成人 AML-NK 初诊时检测了这两个基因的表达水平，并研究了它们的预后潜力。
大约三分之一的患者检测到 BAALC 和 MN1 的表达，并且这两个基因之间存在正相关。BAALC /或 MN1 状态与 FLT3-ITD 突变的存在无关，但与 NPM1 状态呈强相关（P<.001）。因此，在 BAALC /或 MN1 患者中，最常见的是具有中等预后的 FLT3-ITD /NPM1 双阴性患者。当将 BAALC /或 MN1 患者分为 BAALC /BAALC（21/21）和 MN1 /MN1（21/22）组时，我们发现 BAALC /或 MN1 患者的完全缓解率有下降的趋势。此外，生存分析表明，BAALC /或 MN1 患者无病生存期和总生存期（OS）较短。在缺乏可靠预后标志物的 FLT3-ITD /NPM1 组患者中，预后影响最为显著，BAALC /或 MN1 患者的 OS 仅为 5 个月，而 BAALC /或 MN1 患者的 OS 为 25 个月。
这些发现表明，BAALC 和 MN1 的表达水平可用于更精确地对 AML-NK 患者进行风险分层，尤其是对 FLT3-ITD /NPM1 患者进行分层，将这一中危组转变为预后不良的组。
