ABSTRACT
OBJECTIVE： To provide reference for reasonable selection of tyrosine kinase inhibitors （TKI） in chronic myeloid leukemia （CML） patients with BCR-ABL35INS mutation. METHODS： Using “BCR-ABL insertional mutation” “ABL1 35ins mutation” “BCR-ABL c.1423_1424ins35” “ABL1 p.C475Tyrfs*11” as keywords， retrieved from CNKI， Wanfang database， Medline and COSMIC database， BCR-ABL35INS mutation CML patients were summarized and analyzed in respects of general information and treatment （treatment plan， patient compliance and drug withdrawal）， therapeutic effect （molecular biological mitigation and disease progress） and safety data （ADR） during 2007-2018. RESULTS： Totally 9 related literatures were included， involving 70 patients with BCR-ABL35INS mutation， all of them were foreign cases. Among them， 39 cases were male and 31 cases were female， with a median age of 49.2 years. The median time from the diagnosis of CML to the detection of BCR-ABL35INS mutation was 19 months. After detecting gene mutation， 39 cases were treated with imatinib （initial dose of 400 mg， po， once a day）， and molecular biological remission was achieved in 5 patients （12.9％）； 15 cases （38.5％） had molecular biological response but had disease progression； 8 patients （20.5％） had no response. Seventeen patients were treated with dasatinib （100 mg， po， once a day or 2 divided dose）， and 8 cases （47.1％） achieved molecular biological response. Twenty-one patients were treated with nilotinib （400 mg， po， 2 divided dose）， and 3 patients （14.3％） achieved molecular biological response； 2 patients achieved molecular biological response， but the disease progressed. Seven， three and seven of these patients stopped taking drugs due to adverse reactions， accounting for 17.9％， 17.6％ and 33.3％ respectively. All the ADRs were classified as grade 3-4 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events， and most of them were hematological toxicity. CONCLUSIONS： CML patients with BCR-ABL35INS mutation are less likely to achieve molecular response on imatinib therapy but are more sensitive to dashatinib. In the course of treatment， we should strengthen the monitoring of blood system and other related indicators to ensure the safety and effectiveness of drug use.
ABSTRACT
The gene for tyrosinase has been mapped to the long arm of chromosome 11 at 11q14-21. The gene is at least 50Kb in length and its coding region is divided into five exons. Until now several mutations of the tyrosinase gene have been identifed in patient with typical oculocutaneous albinism (OCA) who are responsible for tyrosinase negative OCA. It may be possible to determine the types of OCA by measuring the hairbulb tyrosinase activity. Hairbulb tyrosinase activity was examined in a Korean albino to determine the type of OCA. And also tyrosinase assay was carried out in normally pigmented individuals and all members of a Korean albino's family to examine the tyrosinase activities. Five exons of tyrosinase gene from a Korean albino were amplified by polymerase chain reaction. Each amplified exon segments were independently subcloned and DNA sequences of clones were determined. The results obtained were as follows : 1. A Korean albino had no measurable hairbulb tyrosinase activity and was identified as type IA (tyrosinase negative) oculocutaneous albinism. 2. Normally pigmented individuals had different ranges of hairbulb tyrosinase activity. 3. A Korean albino had two single base insertions within exon V (between 337bp and 338bp, 353bp and 354bp) of tyrosinase gene. These insertional mutations might disrupt tyrosinase function and were associated with a total lack of melanin biosynthesis.