検査と技術51巻9号

2023年09月発行

増大号 匠から学ぶ　血栓止血検査ガイド 5章　疾患まとめ

急性前骨髄球性白血病（APL）とDIC

著者： 池添隆之¹

所属機関： ¹福島県立医科大学血液内科学講座

ページ範囲：P.1093 - P.1096

APLの疾患概念

　急性前骨髄球性白血病（acute promyelocytic leukemia：APL）は，急性骨髄性白血病（acute myeloid leukemia：AML）の約10％を占める，まれな造血器悪性腫瘍である．転座型染色体異常t（15;17）の結果形成されるPML::RARαキメラ遺伝子が，APLの病態形成に中心的な役割を果たす．初発APL153例に対して行ったシーケンス解析によると，約70％の症例でFLT3，WT1，KRASやNRASのいずれかに遺伝子変異を認めた一方，AMLで高頻度にみられるDNMT3A，NPM1，TET2やRUNX1にはほとんど異常を認めず，APLは細胞遺伝学的にAMLとは明らかに異なる造血器腫瘍である^1）．

参考文献

1）Madan V, et al. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia. Leukemia 2016; 30: 1672-1681.

2）Yan J, et al. PML/RARalpha fusion protein transactivates the tissue factor promoter through a GAGC-containing element without direct DNA association. Proc Natl Acad Sci U S A. 2010; 107: 3716-3721.

3）Ikezoe T. Advances in the diagnosis and treatment of disseminated intravascular coagulation in haematological malignancies. Int J Hematol. 2021; 113: 34-44.

4）池添隆之．急性前骨髄球性白血病（APL）に合併したDICの治療戦略．Land-Mark Thromb Haemost．2022；2：71-74．

5）Lavallée VP, et al. Transcriptomic landscape of acute promyelocytic leukemia reveals aberrant surface expression of the platelet aggregation agonist Podoplanin. Leukemia 2018; 32: 1349-1357.

6）Harada-Shirado K, et al. Circulating intranuclear proteins may play a role in development of disseminated intravascular coagulation in individuals with acute leukemia. Int J Hematol. 2020; 111: 378-387.

7）Huang D, et al. Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent fibrinolysis and matrix invasion in acute promyelocytic leukemia. Front Med. 2017; 11: 410-422.

8）Lehmann S, et al. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia 2011; 25: 1128-1134.

9）Park JH, et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood 2011; 118: 1248-1254.

10）de la Serna J, et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood 2008; 111: 3395-3402.

11）Breccia M, et al. Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features. Leukemia 2007; 21: 79-83.

12）DIC診断基準作成委員会．日本血栓止血学会DIC診断基準　2017年版．日血栓止血会誌．2017；28：369-391．

13）Saito H, et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase Ⅲ, randomized, double-blind clinical trial. J Thromb Haemost. 2007; 5: 31-41.

14）Matsushita T, et al. Thrombomodulin alfa treatment in patients with acute promyelocytic leukemia and disseminated intravascular coagulation: a retrospective analysis of an open-label, multicenter, post-marketing surveillance study cohort. Thromb Res. 2014; 133: 772-781.

15）Ikezoe T, et al. Recombinant human soluble thrombomodulin safely and effectively rescues acute promyelocytic leukemia patients from disseminated intravascular coagulation. Leuk Res. 2012; 36: 1398-1402.

16）Avvisati G, et al. Tranexamic acid for control of haemorrhage in acute promyelocytic leukaemia. Lancet 1989; 2: 122-124.

17）Brown JE, et al. All-trans retinoic acid (ATRA) and tranexamic acid: a potentially fatal combination in acute promyelocytic leukaemia. Br J Haematol. 2000; 110: 1010-1012.