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Views: 0 Author: Site Editor Publish Time: 2024-09-11 Origin: Site
Genes and Types The BCR-ABL fusion gene is formed by the fusion of the ABL gene on chromosome 9 and the BCR gene on chromosome 22. Depending on the breakage site, BCR-ABL p210 (E13A2 or E14A2), p190 (typically E1A2), p230 (E19A2), and other rare types such as E6A2 and E18A2 can be formed. BCR-ABL and Disease Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, chronic myeloid leukemia, or chronic granulocytic leukemia, is a myeloproliferative neoplasm characterized by dysregulated production and uncontrolled proliferation of mature and immature granulocytes, with generally normal cell differentiation. CML has a hallmark cytogenetic abnormality, the Philadelphia chromosome (Ph), formed by t(9;22)(q34;q11). At the molecular level, it forms the BCR-ABL fusion gene, which is found in over 95% of CML cases. Acute lymphocytic leukemia (ALL) is a type of hematologic malignancy characterized by the malignant proliferation of prolymphocytes. BCR-ABL+ALL accounts for 20%-30% of adult ALL. Conventional chemotherapy is ineffective. Tyrosine kinase inhibitors (TKIs) are targeted drugs for this fusion protein. Combining TKIs with chemotherapy can significantly improve the prognosis of BCR-ABL+ALL patients, achieving a CR rate exceeding 90% and a 5-year overall survival (OS) rate of 40%-60%. Therefore, the detection and diagnosis of the BCR-ABL fusion gene is extremely important. Drug Resistance and Mutation Approximately 50%-90% of BCR-ABL tyrosine kinase inhibitor (TKI) resistance is due to mutations in the ABL kinase domain. These mutations are primarily concentrated in the phosphate-binding loop (P-loop; M244, G250, Q252, Y253, E255), gatekeeper residues (T315, F317), SH2 contacts and C-lobes (M351, F359), and the activation loop (H396). Research has found that point mutations in the BCR-ABL kinase are key contributors to resistance to imatinib (IM) and dasatinib (DA) in CML patients, with the T315I mutation being the most important. Also known as the "gatekeeper mutation," the T315I mutation involves a single C-to-T substitution at position 944 of the ABL kinase residue, resulting in a threonine-to-isoleucine substitution at position 315. This mutation can enhance the activity of ABL kinase, while blocking the ATP binding site on the kinase, destroying the formation of key hydrogen bonds, and increasing the steric hindrance between the drug and the kinase, causing resistance to the first two generations of TKIs. Detection method The detection techniques for the BCR-ABL fusion gene include fluorescent in situ hybridization (FISH), fluorescent reverse transcription polymerase chain reaction (RT-PCR), and digital polymerase chain reaction (dPCR). CB-Gene CB-Gene Bio can provide diagnostic standards for BCR-ABL1 fusion and fusion + mutation types to ensure the detection limit, sensitivity and stability of the diagnostic method. AI-Edigene® BCR-ABL1 (E13-E2) Translocation with ABL1 p.T315I Reference Standard Plus CBP10519 Figure 3. BCR-ABL1 (E13-E2) Translocation Sanger Figure 4. ABL1 p.T315I Sanger AI-Edigene® BCR-ABL1 (E13-E2) Fusion with ABL1 p.T315I Plus CBP20222R Figure 5. BCR-ABL1 (E13-E2) Fusion Figure 6. ABL1 p.T315I AI-Edigene® BCR-ABL1 (E13-E2) Fusion without ABL1 p.T315I plus CBP20223R Figure 7. BCR-ABL1 (E13-E2) Fusion Figure 8. ABL1 p.T315T
