MDSにおける体細胞変異と予後への影響  [in Japanese] Significance of somatic mutations on the prognosis of myelodysplastic syndromes  [in Japanese]

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Author(s)

    • 吉里 哲一 YOSHIZATO Tetsuichi
    • 京都大学大学院医学研究科 腫瘍生物学講座 Kyoto University, Department of Pathology and Tumor Biology, Graduate School of Medicine

Abstract

<p>網羅的遺伝子解析技術の飛躍的な進歩とともに,骨髄異形成症候群におけるゲノム異常の解明が進み,スプライシング因子やエピジェネティック制御因子などの変異が高頻度に認められることが明らかになった。これら体細胞変異の骨髄異形成症候群の病型や予後に対する影響も評価されており,スプライシング因子である<i>SF3B1</i>の変異は鉄芽球性貧血と強く関連し,良好な予後を示す。一方,<i>TP53</i>変異は骨髄異形成症候群の5~10%の症例で認められるが,染色体異常を高頻度に合併し,<i>TP53</i>変異を有する症例の予後は不良であり,同種造血幹細胞移植を実施しても,移植後の早期再発が多く不良な転機を取る。本稿で述べるように変異の予後や治療反応性に対する知見は続々と増えており,今後,骨髄異形成症候群の治療方針決定の際に臨床情報に加えて,ゲノム異常も考慮して判断することが重要になると考えられる。</p>

<p>During the past decade, substantial advances have been made in our understanding of the genetic basis of myelodysplastic syndromes (MDS), wherein a spectrum of major mutational targets associated with MDS, such as splicing factors and epigenetic regulators, has been revealed. The impact of mutations in these genes on disease subtypes and prognosis has also been evaluated. A mutation in <i>SF3B1</i>, one of the spliceosome machinery components, defines a distinct MDS subtype characterized by ring sideroblasts, indolent clinical course, and favorable clinical outcome. On the other hand, mutation in <i>TP53</i> is observed in 5-10% of cases and is associated with an aggressive phenotype, higher frequency of copy number abnormalities, and poor prognosis. Even in the setting of hematopoietic stem-cell transplantation, patients with <i>TP53</i> mutations, particularly in cases where complex cytogenetic abnormalities were also present, showed extremely poor prognosis. Because the importance of molecular profiles in the prognosis of MDS is being better understood, treatment decisions may begin incorporating this information in addition to conventional clinical factors.</p>

Journal

  • Rinsho Ketsueki

    Rinsho Ketsueki 59(8), 1078-1085, 2018

    The Japanese Society of Hematology

Codes

  • NII Article ID (NAID)
    130007472195
  • NII NACSIS-CAT ID (NCID)
    AN00252940
  • Text Lang
    JPN
  • ISSN
    0485-1439
  • NDL Article ID
    029225825
  • NDL Call No.
    Z19-295
  • Data Source
    NDL  J-STAGE 
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