白血病に限らず、悪性腫瘍は遺伝子の異常により引き起こされます。白血病で繰り返し起きる遺伝子異常を確認することは、予後予測に重要であるばかりでなく、治療選択にも直結する時代が始まっています。私が初めて米国血液学会に参加した2004年、世界ではすでにFLT3-ITD, NPM1, CEBPA変異の有無で正常核型のAMLの予後が層別化できることが発表されていました。それから15年たった現在の日本において、未だにこれらの遺伝子変異全てを保険診療で調べることはできません。当グループでは北日本血液研究会（NJHSG）の自主臨床研究「急性白血病における遺伝子変異と治療反応性・白血病発症機序の解明」、通称：北海道白血病ネット(Hokkaido Leukemia Net)を主催しています。全道17施設の急性白血病検体を収集し、予後に関わる変異解析を行い主治医に返却しています。のべ700例を超える白血病サンプルを所有し、新規の登録は年間170例を超えています。これは欧米の大規模コホートに匹敵する症例規模であり、毎年予後追跡データを更新しています。この活動を通じて、臨床に貢献すると共に、新たな知見を生み出していきます。

白血病に関するテーマ：

1. 急性骨髄性白血病における遺伝子変異の発生機序
2. 急性骨髄性白血病における分子標的薬耐性機序の解明とその克服
3. 急性リンパ性白血病におけるIKZF1欠失検出法の開発（IKZF1欠失FISH）

また、患者様との巡り会いから、導かれるように血小板研究も行い成果を上げつつあります。

血小板に関するテーマ：

1. 巨大血小板を伴う先天性血小板減少をきたす新規インテグリン変異とその機能解析
2. アナグレリドによる血小板減少効果の解析
3. 家族性血小板増多症に関わる変異解析

当グループでは目の前にある臨床上の疑問に科学的に答えを出すことを目標に、様々なテーマに取り組んでいます。テーマごとに共同研究の輪を広げ、限られた時間、限られた資金で効率的な研究を進めます。大学院生には臨床論文１本、基礎論文１本を目指してもらっています。やる気のある若手の参加をお待ちしています。

（文責：小野澤）

Group publication list (since 2014)

1. 1. A novel nutritional index "simplified CONUT" and the disease risk index independently stratify prognosis of elderly patients with acute myeloid leukemia.
   Senjo H, Onozawa M, Hidaka D, Yokoyama S, Yamamoto S, Tsutsumi Y, Haseyama Y, Nagashima T, Mori A, Ota S, Sakai H, Ishihara T, Miyagishima T, Kakinoki Y, Kurosawa M, Kobayashi H, Iwasaki H, Hashimoto D, Kondo T, Teshima T. Sci Rep. 2020 Nov 10;10(1):19400.
2. 2. Short-term treatment with imetelstat sensitizes hematopoietic malignant cells to a genotoxic agent via suppression of the telomerase-mediated DNA repair process.
   Hidaka D, Onozawa M, Miyashita N, Yokoyama S, Nakagawa M, Hashimoto D, Teshima T.Leuk Lymphoma. 2020 Nov;61(11):2722-2732.
3. 3. Anagrelide modulates proplatelet formation resulting in decreased number and increased size of platelets
   Naohiro Miyashita, Masahiro Onozawa, Shota Yokoyama, Daisuke Hidaka, Koji Hayasaka, Shinji Kunishima, Takanori Teshima
   HemaSphere. 2019 Aug 7;3(4):e268.
4. 4. Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation.
   Toffalori C, Zito L, Gambacorta V, Riba M, Oliveira G, Bucci G, Barcella M, Spinelli O, Greco R, Crucitti L, Cieri N, Noviello M, Manfredi F, Montaldo E, Ostuni R, Naldini MM, Gentner B, Waterhouse M, Zeiser R, Finke J, Hanoun M, Beelen DW, Gojo I, Luznik L, Onozawa M, Teshima T, Devillier R, Blaise D, Halkes CJM, Griffioen M, Carrabba MG, Bernardi M, Peccatori J, Barlassina C, Stupka E, Lazarevic D, Tonon G, Rambaldi A, Cittaro D, Bonini C, Fleischhauer K, Ciceri F, Vago L.
   Nat Med. 2019 Apr;25(4):603-611.
5. 5. Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT.
   Noviello M, Manfredi F, Ruggiero E, Perini T, Oliveira G, Cortesi F, De Simone P, Toffalori C, Gambacorta V, Greco R, Peccatori J, Casucci M, Casorati G, Dellabona P, Onozawa M, Teshima T, Griffioen M, Halkes CJM, Falkenburg JHF, Stölzel F, Altmann H, Bornhäuser M, Waterhouse M, Zeiser R, Finke J, Cieri N, Bondanza A, Vago L, Ciceri F, Bonini C. Nat Commun. 2019 Mar 25;10(1):1065.
6. 6. Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas.
   Kataoka K, Miyoshi H, Sakata S, Dobashi A, Couronné L, Kogure Y, Sato Y, Nishida K, Gion Y, Shiraishi Y, Tanaka H, Chiba K, Watatani Y, Kakiuchi N, Shiozawa Y, Yoshizato T, Yoshida K, Makishima H, Sanada M, Onozawa M, Teshima T, Yoshiki Y, Ishida T, Suzuki K, Shimada K, Tomita A, Kato M, Ota Y, Izutsu K, Demachi-Okamura A, Akatsuka Y, Miyano S, Yoshino T, Gaulard P, Hermine O, Takeuchi K, Ohshima K, Ogawa S.
   Leukemia.2019 Jan 25.
7. 7. Quantitative detection of IKZF1 deletion by digital PCR in patients with acute lymphoblastic leukemia.
   Hashiguchi J, Onozawa M, Okada K, Amano T, Hatanaka KC, Nishihara H, Sato N, Teshima T.
   Int J Lab Hematol. 2019 Apr;41(2):e38-e40.
8. 8. Wilms Tumor 1 Expression at Diagnosis Correlates With Genetic Abnormalities and Polymorphism But Is Not Independently Prognostic in Acute Myelogenous Leukemia: A Hokkaido Leukemia Net Study.
   Hidaka D, Onozawa M, Hashiguchi J, Miyashita N, Kasahara K, Fujisawa S, Hayase E, Okada K, Shiratori S, Goto H, Sugita J, Nakagawa M, Hashimoto D, Kahata K, Endo T, Yamamoto S, Tsutsumi Y, Haseyama Y, Nagashima T, Mori A, Ota S, Sakai H, Ishihara T, Imai K, Miyagishima T, Kakinoki Y, Kurosawa M, Kobayashi H, Iwasaki H, Shimizu C, Kondo T, Teshima T.
   Clin Lymphoma Myeloma Leuk. 2018 Nov;18(11):e469-e479.
9. 9. The association between the incidence of intestinal graft-vs-host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation.
   Hidaka D, Hayase E, Shiratori S, Hasegawa Y, Ishio T, Tateno T, Okada K, Goto H, Sugita J, Onozawa M, Nakagawa M, Kahata K, Endo T, Hashimoto D, Teshima T.
   Clin Transplant. 2018 Sep;32(9):e13361.
10. 10. Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia.
    Hashiguchi J, Onozawa M, Oguri S, Fujisawa S, Tsuji M, Okada K, Nakagawa M, Hashimoto D, Kahata K, Kondo T, Shimizu C, Teshima T.
    J Mol Diagn. 2018 Jul;20(4):446-454.
11. 11. Re-infection of toxoplasma gondii after HSCT presenting lymphadenopathy resembling recurrence of lymphoma.
    Hashiguchi J, Onozawa M, Naka T, Hatanaka KC, Shiratori S, Sugita J, Fujimoto K, Matsuno Y, Teshima T.
    Transpl Infect Dis. 2018 Mar 30:e12892.
12. 12. A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction.
    Miyashita N, Onozawa M, Hayasaka K, Yamada T, Migita O, Hata K, Okada K, Goto H, Nakagawa M, Hashimoto D, Kahata K, Kondo T, Kunishima S, Teshima T.
    Ann Hematol. 2018 Apr;97(4):629-640.
13. 13. Disseminated toxoplasmosis after hematopoietic stem cell transplantation showing unusual magnetic resonance images.
    Tateno T, Onozawa M, Hashiguchi J, Ishio T, Yuzawa S, Matsuoka S, Kosugi-Kanaya M, Okada K, Shiratori S, Goto H, Kimura T, Sugita J, Nakagawa M, Hashimoto D, Kahata K, Fujimoto K, Endo T, Kondo T, Tanaka S, Hashino S, Teshima T.
    Transpl Infect Dis. 2017 Aug;19(4).
14. 14. Risk factors of human herpesvirus 6 encephalitis/myelitis after allogeneic hematopoietic stem cell transplantation.
    Miyashita N, Endo T, Onozawa M, Hashimoto D, Kondo T, Fujimoto K, Kahata K, Sugita J, Goto H, Matsukawa T, Hashino S, Teshima T.
    Transpl Infect Dis. 2017 Jun;19(3).
15. 15. Templated Sequence Insertion Polymorphisms in the Human Genome.
    Onozawa M, Aplan PD.
    Front Chem. 2016 Nov 16;4:43.
16. 16. Cytogenetically Unrelated Clones in Acute Myeloid Leukemia Showing Different Responses to Chemotherapy.
    Kasahara K, Onozawa M, Miyashita N, Yokohata E, Yoshida M, Kanaya M, Kosugi-Kanaya M, Takemura R, Takahashi S, Sugita J, Shigematsu A, Takahata M, Fujisawa S, Hashimoto D, Fujimoto K, Endo T, Kondo T, Teshima T.
    Case Rep Hematol. 2016;2016:2373902.
17. 17. Landscape of insertion polymorphisms in the human genome.
    Onozawa M, Goldberg L, Aplan PD.
    Genome Biol Evol. 2015 Mar 4;7(4):960-8.
18. 18. DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier.
    Santos MA, Faryabi RB, Ergen AV, Day AM, Malhowski A, Canela A, Onozawa M, Lee JE, Callen E, Gutierrez-Martinez P, Chen HT, Wong N, Finkel N, Deshpande A, Sharrow S, Rossi DJ, Ito K, Ge K, Aplan PD, Armstrong SA, Nussenzweig A.
    Nature. 2014 Oct 2;514(7520):107-11.
19. 19. Repair of DNA double-strand breaks by templated nucleotide sequence insertions derived from distant regions of the genome.
    Onozawa M, Zhang Z, Kim YJ, Goldberg L, Varga T, Bergsagel PL, Kuehl WM, Aplan PD.
    Proc Natl Acad Sci U S A. 2014 May 27;111(21):7729-34.