Kyoto University · 의학
Hideki Makishima 교수의 연구실은 골수형성이상증후군(MDS)과 만성골수성백혈병(CML)을 비롯한 골수성 혈액암의 분자 기반 병태생리학을 연구합니다. 특히 스플라이싱 유전자(SF3B1, TET2, ASXL1 등)의 돌연변이와 복수의 타이로신 키나제 조절 유전자(CBL, CBLB)의 기능 저하가 혈액세포 이상성과 악성 퇴행에 기여하는 메커니즘을 규명하고자 합니다. 또한 복수의 유전적 이상이 발생하지만 복수 수준의 변화가 없는 손실 이형성(복수 중성 손실 이형성, uniparental disomy)이 암의 클론 성장에 기여할 수 있음을 밝혀내며, 전장 게놈 분석 기반의 새로운 암 유전학 접근법을 선도하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Myelodysplastic syndromes (MDSs) are chronic and often progressive myeloid neoplasms associated with remarkable heterogeneity in the histomorphology and clinical course. Various somatic mutations are involved in the pathogenesis of MDS. Recently, mutations in a gene encoding a spliceosomal protein, SF3B1, were discovered in a distinct form of MDS with ring sideroblasts. Whole exome sequencing of 15 patients with myeloid neoplasms was performed, and somatic mutations in spliceosomal genes were id
Mutations in the Cbl family RING finger domain or linker sequence constitute important pathogenic lesions associated with not only preleukemic CMML, JMML, and other MPN, but also progression to AML, suggesting that impairment of degradation of activated tyrosine kinases constitutes an important cancer mechanism.
Progression of chronic myelogenous leukemia (CML) to accelerated (AP) and blast phase (BP) is because of secondary molecular events, as well as additional cytogenetic abnormalities. On the basis of the detection of JAK2, CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations in myelodysplastic/myeloproliferative neoplasms, we hypothesized that they may also contribute to progression in CML. We screened these genes for mutations in 54 cases with CML (14 with chronic phase, 14 with AP, 20 with myeloid, and
The systematic application of new genome-wide single nucleotide polymorphism arrays has demonstrated that somatically acquired regions of loss of heterozygosity without changes in copy number frequently occur in many types of cancer. Until recently, the ubiquity of this type of chromosomal defect had gone unrecognized because it cannot be detected by routine cytogenetic technologies. Random and recurrent patterns of copy-neutral loss of heterozygosity, also referred to as uniparental disomy, can
