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International Journal of Hematology

, Volume 108, Issue 3, pp 274–281 | Cite as

Cell dynamics during differentiation therapy with all-trans retinoic acid in acute promyelocytic leukemia

  • Kazuyuki Sato
  • Hirotaka Sakai
  • Yusuke Saiki
  • Akiko Uchida
  • Yu Uemura
  • Satoshi Yokoi
  • Yuka Tsuruoka
  • Yuji Nishio
  • Manabu Matsunawa
  • Yoshinori Suzuki
  • Yasushi Isobe
  • Masayuki Kato
  • Naoto Tomita
  • Yasuyuki Inoue
  • Ikuo Miura
Original Article
  • 105 Downloads

Abstract

The introduction of all-trans retinoic acid (ATRA) has made acute promyelocytic leukemia (APL) a curable disease; however, early death prior to the completion of treatment remains a problem. In quantitative evaluation of response to ATRA treatment, lymphocytes must be excluded as they do not originally have t(15;17). We categorized peripheral blood leukocytes by nuclear morphology into polymorphonuclear cells (PMNs) comprising segmented granulocytes, and non-polymorphonuclear cells (NPMs) which includes lymphocytes, monocytes, band cells, and immature myeloid cells. We consecutively evaluated the ratio of t(15;17)-positive cells using fluorescence in situ hybridization in eight newly diagnosed patients with APL. We confirmed the differentiation of APL cells until cytogenetic complete remission; the association of a decrease of t(15;17)-positive NPMs and an increase of t(15;17)-positive PMNs was followed by a decrease of t(15;17)-positive PMNs. The kinetic pattern of t(15;17)-positive NPMs and PMNs was consistent in most patients, irrespective of leukocyte counts at diagnosis, additional chromosomal changes, and ATRA with or without chemotherapies. Kinetic analysis enables us to evaluate treatment response and the recovery of normal hematopoiesis in individuals.

Keywords

Fluorescence in situ hybridization t(15;17) PMLRARA Early death 

Notes

Compliance with ethical standards

Conflict of interest

I. M. is a consultant for SRL, Inc.

References

  1. 1.
    De Thé H, Chen Z. Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat Rev Cancer. 2010;10:775–83.CrossRefPubMedGoogle Scholar
  2. 2.
    Ablain J, De Thé H. Retinoic acid signaling in cancer: the parable of acute promyelocytic leukemia. Int J Cancer. 2014;135:2262–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Arber DA, Brunning RD, Le Beau MM, Falini B, Vardiman JW, Porvit A, et al. Acute myeloid leukaemia with recurrent genetic abnormalities. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2017. pp. 130–49.Google Scholar
  4. 4.
    Wang ZY, Sun GL, Lu JX, Gu LJ, Huang ME, Chen SR. Treatment of acute promyelocytic leukemia with all-trans retinoic acid in China. Nouv Rev Fr Hematol. 1990;32:34–6.PubMedGoogle Scholar
  5. 5.
    Fenaux P, Le Deley MC, Castaigne S, Archimbaud E, Chomienne C, Link H, et al. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group. Blood. 1993;82:3241–49.PubMedGoogle Scholar
  6. 6.
    Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Woods WG, et al. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood. 2002;100:4298–302.CrossRefPubMedGoogle Scholar
  7. 7.
    Mandelli F, Latagliata R, Avvisati G, Fazi P, Rodeghiero F, Leoni F, et al. Treatment of elderly patients (> or = 60 years) with newly diagnosed acute promyelocytic leukemia. Results of the Italian multicenter group GIMEMA with ATRA and idarubicin (AIDA) protocols. Leukemia. 2003;17:1085–90.CrossRefPubMedGoogle Scholar
  8. 8.
    Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004;103:1237–43.CrossRefPubMedGoogle Scholar
  9. 9.
    Testi AM, Biondi A, Lo Coco F, Moleti ML, Giona F, Vignetti M, et al. GIMEMA-AIEOPAIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children. Blood. 2005;106:447–53.CrossRefPubMedGoogle Scholar
  10. 10.
    Asou N, Kishimoto Y, Kiyoi H, Okada M, Kawai Y, Tsuzuki M, et al. A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RARalpha transcript after consolidation therapy: the Japan Adult Leukemia Study Group (JALSG) APL97 study. Blood. 2007;110:59–66.CrossRefPubMedGoogle Scholar
  11. 11.
    Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008;111:2505–15.CrossRefPubMedGoogle Scholar
  12. 12.
    Lehmann S, Ravn A, Carlsson L, Antunovic P, Deneberg S, Möllgård L, et al. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia. 2011;25:1128–34.CrossRefPubMedGoogle Scholar
  13. 13.
    Park JH, Qiao B, Panageas KS, Schymura MJ, Jurcic JG, Rosenblat TL, et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood. 2011;118:1248–54.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    McClellan JS, Kohrt HE, Coutre S, Gotlib JR, Majeti R, Alizadeh AA, et al. Treatment advances have not improved the early death rate in acute promyelocytic leukemia. Haematologica. 2012;97:133–6.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Lengfelder E, Hanfstein B, Haferlach C, Braess J, Krug U, Spiekermann K, et al. Outcome of elderly patients with acute promyelocytic leukemia: results of the German Acute Myeloid Leukemia Cooperative Group. Ann Hematol. 2013;92:41–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Micol JB, Raffoux E, Boissel N, Lengliné E, Canet E, Daniel MT, et al. Management and treatment results in patients with acute promyelocytic leukaemia (APL) not enrolled in clinical trials. Eur J Cancer. 2014;50:1159–68.CrossRefPubMedGoogle Scholar
  17. 17.
    McCulloch D, Brown C, Iland H. Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives. Onco Targets Ther. 2017;10:1585–601.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    McGowan-Jordan J, Simons A, Schmid M. International system for human cytogenomic nomenclature. Basel: Kargener; 2016.Google Scholar
  19. 19.
    De La Serna J, Montesinos P, Vellenga E, Rayón C, Parody R, León A, 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;111:3395–402.CrossRefPubMedGoogle Scholar
  20. 20.
    Cull EH, Altman JK. Contemporary treatment of APL. Curr Hematol Malig Rep. 2014;9:193–201.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sanz MA, Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. Blood. 2014;123:2777–82.CrossRefPubMedGoogle Scholar
  22. 22.
    Luesink M, Pennings JL, Wissink WM, Linssen PC, Muus P, Pfundt R, et al. Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome. Blood. 2009;114:5512–21.CrossRefPubMedGoogle Scholar
  23. 23.
    Tallman MS, Lo-Coco F, Kwaan HC, Sanz MA, Gore SD. Early death in patients with acute promyelocytic leukemia. Proceedings from a live roundtable at the 2010 American Society of Hematology Annual Meeting, December 4–7, 2010, Orlando, Florida. Clin Adv Hematol Oncol 2011;9: 1–16.Google Scholar
  24. 24.
    Testa U, Lo-Coco F. Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients. Ann Hematol. 2016;95:673–80.CrossRefPubMedGoogle Scholar
  25. 25.
    De Botton S, Chevret S, Sanz M, Dombret H, Thomas X, Guerci A, et al; European APL Group. Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL) do not confer poor prognosis: results of APL 93 trial. Br J Haematol. 2000;111:801–6.PubMedGoogle Scholar
  26. 26.
    Cervera J, Montesinos P, Hernández-Rivas JM, Calasanz MJ, Aventín A, Ferro MT, et al. Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Haematologica. 2010;95:424–31.CrossRefPubMedGoogle Scholar
  27. 27.
    De Braekeleer E, Douet-Guilbert N, De Braekeleer M. RARA fusion genes in acute promyelocytic leukemia: a review. Expert Rev Hematol. 2014;7:347–57.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2018

Authors and Affiliations

  • Kazuyuki Sato
    • 1
  • Hirotaka Sakai
    • 1
  • Yusuke Saiki
    • 1
  • Akiko Uchida
    • 1
  • Yu Uemura
    • 1
  • Satoshi Yokoi
    • 1
  • Yuka Tsuruoka
    • 1
  • Yuji Nishio
    • 1
  • Manabu Matsunawa
    • 1
  • Yoshinori Suzuki
    • 1
  • Yasushi Isobe
    • 1
  • Masayuki Kato
    • 1
  • Naoto Tomita
    • 1
  • Yasuyuki Inoue
    • 1
  • Ikuo Miura
    • 1
  1. 1.Division of Hematology and Oncology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan

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