Kyoto University · Medicine
Professor Hideki Makishima's research lab specializes in the molecular genetics and pathogenesis of myeloid neoplasms, with a focus on identifying somatic mutations and chromosomal abnormalities underlying diseases such as myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), and myeloproliferative neoplasms (MPN). The lab employs advanced genomic technologies, including whole-exome sequencing and single-nucleotide polymorphism (SNP) arrays, to uncover mutations in spliceosomal genes (e.g., SF3B1, U2AF1), tyrosine kinase regulators (e.g., CBL, CBLB), and epigenetic modifiers (e.g., TET2, ASXL1, IDH1/2) that drive disease progression. A key research direction involves understanding the functional impact of copy-neutral loss of heterozygosity (uniparental disomy) and its role in clonal evolution and leukemogenesis. The lab integrates genomic profiling with clinical phenotypes to elucidate disease mechanisms and improve diagnostic and prognostic stratification.
Figures are computed from collected data and may differ slightly.
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
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