Fusion genes can improve outcomes in B-cell precursor acute lymphoblastic leukemia patients

Fusion genes are initiating factors in the development of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). New BCP-ALL related fusion genes are constantly discovered, but clinical cohort studies on these genes’ characteristics and outcomes are still lacking.

Researchers from the Peking University Institute of Hematology performed a study in which real-time quantitative PCR was used to retrospectively screen novel fusions (Ph-like, ZNF384 and MEF2D fusion genes) in a cohort of newly diagnosed BCP-ALL cases from a Chinese institute, that had undergone testing for classical (BCR-ABL, KMT2A and TCF3-PBX1) fusion genes at diagnosis. In the present study, 12.5% of patients had classical fusions, while 4.4%, 17.2%, and 3.8% of patients had Ph-like, ZNF384, and MEF2D fusions, respectively. According to clinical outcomes, patients were further divided into fusion-defined high-risk groups and standard-risk groups. As a result, fusion defined high-risk independently predicted poor relapse free survival in the entire cohort.

The current study integrated both classical and novel fusion genes to perform risk stratification, and it provided solid data evidence for the prevalence and characteristics of fusion genes in Asian BCP-ALL populations. The detection of fusion genes improves risk stratification in adult Ph-negative BCP-ALL patients, which may facilitate early clinical intervention in high-risk patients to improve outcomes.

融合基因是 B 細胞前體急性淋巴細胞白血病 (BCP-ALL) 發展的起始因素。新的 BCP-ALL 相關融合基因不斷被發現，但仍缺乏對這些基因特徵和結果的臨床隊列研究。

北京大學血液學研究所的研究人員進行了一項研究，其中實時定量 PCR 用於回顧性篩選來自中國研究所的一組新診斷的 BCP-ALL 病例中的新型融合（Ph-like、ZNF384 和 MEF2D 融合基因） ，在診斷時已經對經典（BCR-ABL、KMT2A 和 TCF3-PBX1）融合基因進行了測試。在本研究中，12.5% 的患者有經典融合，而 4.4%、17.2% 和 3.8% 的患者分別有 Ph-like、ZNF384 和 MEF2D 融合。根據臨床結果，將患者進一步分為融合定義的高風險組和標準風險組。因此，融合定義的高風險獨立預測了整個隊列中較差的無復發生存率。

目前的研究整合了經典和新型融合基因進行風險分層，並為亞洲 BCP-ALL 人群中融合基因的流行和特徵提供了可靠的數據證據。融合基因的檢測改善了成人 Ph 陰性 BCP-ALL 患者的風險分層，這可能有助於對高危患者進行早期臨床干預以改善預後。

Reference: Sun K, Wang J, Chen W-M, Xu N, Long L-Y, Wang X, Jiang H, Jiang Q, Huang X-J, Qin Y-Z. Clinical features and outcomes of fusion gene defined adult Ph-negative B-cell precursor acute lymphoblastic leukemia patients: a single institutional report. Bosn J of Basic Med Sci [Internet]. 2022Sep.14 [cited 2022Sep.19];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7851

Editor: Merima Bukva, MPharm