Acute leukemia (AL) is a group of highly heterogeneous hematological malignancies, which can be mainly divided into acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and acute undifferentiated leukemia (mainly refers to mixed phenotype acute leukemia, MPAL). Among which, AML is the most commonly seen AL in adults, around 70% mitigated patients finally relapsed, and developed into refractory leukemia, which led to death due to treatment failure. Morbidity of AML has been increasing on a yearly basis throughout the world.
Accompanied with proposal and development of precision medicine and precision diagnosis, evaluation of diagnosis and treatment results of leukemia no longer solely relies on morphology, molecular biology, flow cytometry and other technologies have been used extensively. With development of molecular biology techniques, an increasing number of fusion gene have been identified, which have proven to be one of the main pathogenesis of AL. Studies indicated that patients with RUNX1- RUNX1T1, PML-RARα and CBFβ-MYH11 can be diagnosed with AML without requirement of archaeocyte ratio of > 20%, fusion gene detection is one of the main bases for the diagnosis and classification of AML. In addition, fusion gene is also a main molecular marker for prognostic stratification, minimal residual disease (MRD) monitoring and targeted therapy of AML patients.
Distribution characteristics of fusion genes of AML patients
·480· Chin J Hematol, June 2021, Vol. 42. No.6
Analysis of fusion gene expression in acute myeloid leukemia
Yan Qi1, Lin Yani2, Huang Xianqi1, Qian Lingzhi2, Ma Jingting2, Zhang Hong2, Chen Long2, Chen Xuejing2, Mi Yingchang1 and Ru Kun2
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College, Tianjin 300020, China;SINO-US Diagnostics Lab,2Tianjin 300385, China
Corresponding author: Ru Kun, Email:kunru@yahoo.com；Mi Yingchang, Email:ychmi@ihcams.ac.cn
Blood Diseases Hospital of Peking Union Medical College (Institute of Hematology of China Academy of Medical Sciences) and SINO-US Diagnostics Lab, Tianjin recently published a research paper ‘Analysis of fusion gene expression in acute myeloid leukemia’ on Chinese Journal of Hematology. The study used leukemia fusion genes (Q51)Screening Kit (Xiamen Zeesan,China), and conducted retrospective analysis of 52 fusion genes in 4192 patients with preliminarily diagnosed of AML in our country. The results of the analysis showed that the fusion gene positivity rate was 46.47%, which was significantly higher than the studies of foreign scholars (22.82%, 38.80%, p＜0.001) and close to that reported by Chinese scholar (41.21%). In addition, the positive rate of different fusion gene in patients of different age groups in this study was consistent with the general trend of studies by Malaysian scholars. Meanwhile, the fusion gene positivity rate (69.18%) and MLL-associated fusion gene (MLL-FG) positivity rate (15.35%) were significantly higher in pediatric patients than in adult patients (44.76%, 8.36%).
Notably, the study detected six adult patients carrying both fusion genes, accounting for 0.14% of all AML patients and 0.30% of fusion gene positive patients. Three of these cases were double positive for CBFβ-MYH11 and BCR-ABL, and the other three were double positive for PML-RARα and BCR-ABL, DEK-CAN and SET-CAN, TEL-ABL and MLL-ELL, respectively.. The results show that leukemia fusion genes were detected by multiplex fluorescence RT-PCR technique, helping to evaluate the acute degree and typing of leukemia, and making the diagnosis typing of leukemia more scientific and standardized. Besides, RT-PCR can be 5 ~ 8 months earlier than conventional cytological method in the appearance of clinical symptoms, and it can detect one leukemia cell in 1×106 karyocyte, which is more specific and sensitive in the early diagnosis of leukemia..
Detection of rare fusion genes in AML
Routine detection of related fusion genes can provide an important bases for diagnosis, typing, clinical therapy selection and prognosis judgment of AML, and it’s also the basis for the detection of leukemia minimal residual disease (MRD). Numerous clinical studies have shown that fusion genes with high positive rates are important, and screening for less positive fusion genes is equally relevant. For instance, PLZF-RARα and STAT5B-RARα positive patients are insensitive to all-trans-retinoicacid (ATRA) and need to consider combined chemotherapy and haematopoietic stem cell transplantation, and misdetection of gene will affect treatment; fusion gene abnormalities with relatively low positive rate in MLL series also have the clinical significance to indication of poor prognosis for treatment of AML patients. These fusion gene problems will also affect the treatment and prognosis of leukemia
Zeesan leukemia fusion gene detection offers more precise clinical typing
Zeesan Biotech’s leukemia fusion gene (Q51) Screening Kit can screen 52 fusion genes, and the study indicates that the positive rates of fusion genes detected by Q51 are consistent with the domestic literatures; and it can be used for precise typing of MLL, NUP98 and RARα fusion gene families. Q55 fusion gene screening kit introduced in this year further upgraded from Q51. The reagent is in the form of pre-packed dry powder and can screen 55 fusion genes, of which 44 fusion genes can be accurately typed, which can better facilitate accurate diagnostic typing and prognostic judgment, and provide a basis for clinical formulation of treatment plans and strategies.
Precise typing, precision diagnosis and treatment