South Australian Medical Research Institute, The University of Adelaide, Adelaide, SA, Australia.
The University of Adelaide, Adelaide, SA, Australia.
Pathology. 2024 Dec;56(7):931-941. doi: 10.1016/j.pathol.2024.08.001. Epub 2024 Sep 7.
Diagnosis of Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) in the real-world remains challenging because of definitional complexities, the diverse diagnostic techniques available and the cost, expertise and time involved. We summarise evidence for diagnosis of clinically important Ph-like ALL related genomic lesions using fluorescence in situ hybridisation (FISH) targeting only clinically important and actionable lesions, an accessible and cost-effective diagnostic technique. Electronic databases were interrogated using broad MeSH terms for articles reporting a detailed FISH strategy for diagnosis of Ph-like ALL published since 2014, yielding 653 full text articles and abstracts. We searched the National Library of Medicine Databases including PubMed, Medline, Embase, Cochrane and relevant abstracts. We included studies with a primary aim of determining the utility of FISH for Ph-like ALL diagnosis and studies with broader aims demonstrating Ph-like ALL diagnostic algorithms which partially involved FISH. Nineteen studies met inclusion criteria. Evidence for FISH to detect CRLF2 rearrangements in Ph-like ALL is strongly established and evidence for FISH to detect non-CRLF2 lesions is evolving rapidly. We documented 1620 cases of non-CRLF2 Ph-like lesions diagnosed by FISH. Confirmatory side-by-side methods were applied in six studies (246 samples), four of which demonstrated 100% concordance of FISH results with alternative methods, while two studies demonstrated over 70% sensitivity and specificity. Additional studies demonstrated wide utilisation of FISH in Ph-like ALL classification across diverse geographies and ethnicities, with contrasting prevalence, implicating a need for targeted FISH strategies. In real-world cohorts, it may be clinically useful to prioritise limited early FISH in B-cell ALL (B-ALL) diagnostic algorithms to identify Ph-like abnormalities that respond to locally available kinase inhibitors to promote and prioritise broad access to effective targeted treatment. Additional studies are required to provide adequately powered validations and verifications of targeted Ph-like FISH panels to confirm sensitivity and specificity against side-by-side gold standard methods, and to define optimal local approaches.
在实际环境中，由于定义复杂、可用的诊断技术多样以及成本、专业知识和时间的限制，费城染色体样急性淋巴细胞白血病（Ph-样 ALL）的诊断仍然具有挑战性。我们总结了使用荧光原位杂交（FISH）针对临床重要且可操作的病变进行临床重要的 Ph-样 ALL 相关基因组病变诊断的证据，这是一种易于获得且具有成本效益的诊断技术。使用广泛的 MeSH 术语在电子数据库中查询了自 2014 年以来发表的关于详细 FISH 策略用于诊断 Ph-样 ALL 的文章的报告，产生了 653 篇全文文章和摘要。我们在包括 PubMed、Medline、Embase、Cochrane 和相关摘要在内的国家医学图书馆数据库中进行了搜索。我们纳入了以确定 FISH 在 Ph-样 ALL 诊断中的实用性为主要目的的研究，以及以部分涉及 FISH 的 Ph-样 ALL 诊断算法为主要目的的研究。有 19 项研究符合纳入标准。在 Ph-样 ALL 中检测 CRLF2 重排的 FISH 的证据已得到充分确立，并且在检测非 CRLF2 病变的 FISH 方面的证据正在迅速发展。我们记录了 1620 例通过 FISH 诊断的非 CRLF2 Ph-样病变。在 6 项研究（246 例样本）中应用了确认性并排方法，其中 4 项研究表明 FISH 结果与替代方法具有 100%的一致性，而 2 项研究表明具有 70%以上的敏感性和特异性。其他研究表明，FISH 在不同地理位置和种族的 Ph-样 ALL 分类中得到了广泛应用，其流行率存在差异，这表明需要针对特定的 FISH 策略。在实际环境中，在 B 细胞急性淋巴细胞白血病（B-ALL）诊断算法中优先进行早期有限的 FISH 检测，以识别对当地可用激酶抑制剂有反应的 Ph-样异常，从而促进和优先提供广泛的有效靶向治疗，可能具有临床意义。需要进一步的研究提供足够强大的验证，以确认针对侧面对比黄金标准方法的靶向 Ph-样 FISH 面板的敏感性和特异性，并确定最佳的本地方法。
