Chronic Myeloid Leukemia (hereinafter referred to as CML) is a malignancy caused by clonal proliferation of HSCs in bone marrow due to the BCR-ABL fusion gene formed by translocation of chromosomes 9 and 22 in the patient’s body. Its chemotherapy, radiotherapy, and other conventional therapies all yielded poor efficacy, which gave it the name of ‘incurable disease’.
CML treatment and TKI drug resistance
However, accompanied with the marketing of the first Tyrosine Kinase Inhibitor (TKI) in the history of mankind of Imatinib in 2001, the 10-year survival rate of patients with CML increased from less than 50% to 85%-90%, which allowed CML to become a chronic disease like hypertension and diabetes. But certain patients still experienced drug resistance in the course of the TKI treatment process. According to previous studies, 20%-30% of CML patients who received Imatinib therapy had drug resistance in 1 year .
BCR-ABL1 kinase domain mutation is one of the major mechanisms of TKI drug resistance. Accompanied by the extensive use of TKI, drug resistance has received increasing attention. According to research results of Peking University People’s Hospital, over half of the patients with CML resistant to Imatinib, Nilotinib and Dasatinib were detected with BCR-ABL1 mutations, and the proportion of T315I mutation was the highest . Therefore, reasonable selection of TKI based on BCR-ABL1 fusion gene kinase domain mutation detection results has become an important reference in standardized diagnosis and treatment of CML by experts at home and abroad [3-4].
BCR-ABL1 kinase domain mutation detection method
The ideal mutation detection method needs to strike a balance between sensitivity and the correlation between test results and clinical prognosis. Chinese Expert Consensus on the Laboratory Practice of BCR-ABL Tyrosine Kinase Domain Mutation Detection pointed out that direct sequencing is a conventional method to detect ABL mutations in clinical works at the moment. However, direct sequencing is characterized by low sensitivity (only 15%~25%), manpower consumption, low efficiency, and other weaknesses. The currently used NGS method also has the problems of relatively high price and comparatively long reporting cycles.
Zeesan BCR-ABL1 Kinase Domain Mutation Detection Reagent
It covers main mutation sites, and offers convenient operation when used with Zeesan’s proprietary multi-color Melting Curve Analysis (MMCA®), which allow it to present reports on the same day and truly solve clinical pain point!
◆Convenient: four-tube four-color reaction system boasts of easy operation and interpretation
◆Comprehensive: 40 detection sites and coverage of over 91% of ABL kinase mutations
◆Sensitive: sensitivity of 5% that’s higher than the sensitivity of Sanger sequencing and reliable detection results
◆Fast: with operating procedure same to qPCR, it can show results in just 5.5h, which offers shorter time and lower cost in comparison with NGS
Precise genotyping, precise diagnosis and treatment
Shi Dayu, Qin Yaqin, Lai Ruiyun et al, BCR-ABL Variables Associated with BCR-ABL Kinase Domain Mutation in TKI-Resistant Patients with Chronic Myeloid Leukemia [J], Chinese Journal of Hematology, 2020, 41(06):469-476.
Soverini S , Benedittis C D , Mancini M , et al. Mutations in the BCR-ABL1 Kinase Domain and Elsewhere in Chronic Myeloid Leukemia[J]. Clinical lymphoma, myeloma & leukemia, 2015, 15S:S120-S128.
Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013［J］. Blood, 2013, 122（6）:872- 884.
 CMA, Chinese Medical Association, Guidelines for Diagnosis and Treatment of Chronic Myelogenous Leukemia in China(2016)［J］, Chiese Journal of Hematology , 2016, 37（8）: 633-639.