Cytogenetics Department, Seattle Cancer Care Alliance, Seattle, Washington.
Clinical Statistics Department, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Cancer. 2015 Sep 1;121(17):2900-8. doi: 10.1002/cncr.29475. Epub 2015 May 29.
Chromosomal abnormalities are important in the diagnosis and prognosis of patients with acute myeloid leukemia (AML). Genomic microarray techniques detect recurrent copy-neutral loss of heterozygosity (cnLOH) in addition to copy number aberrations. However, the clinical utility has not been fully established. Therefore, in the current study, the authors examined the prognostic impact of acquired cnLOH in patients with AML, including complete remission (CR) rate, duration of CR, and overall survival (OS).
A total of 112 consecutive patients with AML who were undergoing chromosome genomic array testing (CGAT) at the Seattle Cancer Care Alliance were included in the current study. DNA from the bone marrow or blood was analyzed with a microarray platform with both single-nucleotide polymorphism (SNP) probes and non-SNP probes to identify acquired cnLOH. Results were correlated with cytogenetic, molecular, immunophenotypic, and other clinicopathological findings.
Patients with cnLOH demonstrated a shorter duration of CR (hazard ratio, 1.87; P =.04) and worse OS (HR, 1.82; P = .03). Multivariate analyses confirmed the independent predictive value of cnLOH for early disease recurrence (P =.02). These results largely reflected those in patients with intermediate and unfavorable cytogenetics. Most strikingly, 13q cnLOH was found to demonstrate a 6.64-fold higher rate of disease recurrence (P =.006) and 3.45-fold worse OS (P = .02) and was enriched with the FLT3-ITD (Fms-related tyrosine kinase 3-internal tandem duplication) mutation.
CnLOH has important prognostic significance in patients with AML. CGAT can replace imbalance fluorescence in situ hybridization and the authors recommend the routine use of CGAT to detect cnLOH, particularly among patients with intermediate-risk cytogenetics.
染色体异常在急性髓系白血病（AML）患者的诊断和预后中很重要。基因组微阵列技术除了检测拷贝数异常外，还可以检测到复发性的拷贝中性杂合性丢失（cnLOH）。然而，其临床应用尚未完全确立。因此，在目前的研究中，作者研究了 AML 患者获得性 cnLOH 的预后影响，包括完全缓解（CR）率、CR 持续时间和总生存（OS）。
共纳入 112 例在西雅图癌症联盟接受染色体基因组阵列检测（CGAT）的连续 AML 患者。使用包含单核苷酸多态性（SNP）探针和非 SNP 探针的微阵列平台对骨髓或血液中的 DNA 进行分析，以识别获得性 cnLOH。结果与细胞遗传学、分子、免疫表型和其他临床病理发现相关联。
有 cnLOH 的患者 CR 持续时间更短（风险比，1.87；P =.04），OS 更差（HR，1.82；P = .03）。多变量分析证实 cnLOH 对早期疾病复发具有独立的预测价值（P =.02）。这些结果在中危和不良核型的患者中基本一致。最显著的是，13q cnLOH 与疾病复发率增加 6.64 倍（P =.006）和 OS 降低 3.45 倍（P = .02）显著相关，并且与 FLT3-ITD（Fms 相关酪氨酸激酶 3 内部串联重复）突变密切相关。
cnLOH 在 AML 患者中有重要的预后意义。CGAT 可以替代不平衡荧光原位杂交，作者建议常规使用 CGAT 检测 cnLOH，特别是在中危核型的患者中。
