From chloroma to acute promyelocytic leukemia – a historical perspective
Authors:
J. Schwarz
Authors‘ workplace:
Klinický úsek Ústavu hematologi e a krevní transfuze Praha, přednosta doc. MUDr. Petr Cetkovský, Ph. D.
Published in:
Vnitř Lék 2008; 54(7-8): 686-700
Category:
Reviews
Overview
The progressing knowledge on chloroma and chloroleukemia is reviewed. However, it is uneasy to identify with certainty the cases of acute promyelocytic leukemia (APL) among the historical descriptions of chloroma since 1823. In part, this is due to confusion produced by the historical cytological nomenclature – in practice, the leukemic promyelocytes were regarded, quite inaccurately, as a subtype of paramyeloblasts until early 1960’s. The term promyelocytic leukemia first appeared in Naegeli’s text-book in 1931. However, no clinical associations of the morphological description were then given. As a clinico-pathological entity, APL was defined by Hillestad in Norway in 1957 and on a more detailed level, by Bernard et al in France in 1959. However, the descriptions of chloroma by Butterfield in 1909 and of leukemia with panmyelophthisis and defibrination by Risak in 1935 in the German-written literature and the case of chloroma described by Libánský in Czech in 1939 were cases of APL with high probability. Further on, experimental studies leading to the postulation of possible differentiation-inducing therapy of leukemia are reviewed – the importance of introducing of clonal culture of hematopoietic cells in the 1960’s and the proof of the possibility of bypassing the maturation block in the works of Sachs’s group in Rehovot, Israel, is stressed, as well as the later experiments with differentiation inducers in the cell line models in the 1970’s and 1980’s. The first trials with retinoids in therapy of APL are mentioned, along with the interesting background of the French-Chinese collaboration (under the auspices of professors Degos and Wang) in the introduction of retinoids into practice in the second half of the 1980’s. It is discussed how the success of the clinical trials led to enormous progression in the field of molecular genetics of APL, which, in turn, led to development of a new generation of remedies, i.e. to the renaissance of arsenic in the treatment of APL in the 1990’s, among others thanks to the current Chinese minister of health, Chen Zhu.
Key words:
history – chloroma – chloroleukemia – acute promyelocytic leukemia – morphology – differentiation induction – retinoids – ATRA – fusion genes – arsenic
Sources
1. Hynek K, Kadlický R. Zprávy z lékařských spolkův a sjezdů. První odborná schůze českých očních lékařů. Čas Lék Čes 1911: 931–937.
2. Libánský J. Chlorom. Popis případu. Čas Lék Čes 1939; 78: 996–1007.
3. Burns A. Observations on the surgical anatomy of the head and neck. Baltimore: Lucas Publishers 1823.
4. Dock G. Chloroma and its relation to leukæmia. Am J Med Sci 1893; 106: 152–185.
5. King A. A case of chloroma. Monthly J Med Sci 1853; 17: 91.
6. Aran FA. Note sur une forme particulière et encore peu connue de cancer de la dure-mère et des os du crâne (cancer vert, chloroma). Arch Gén Méd 1854; 2: 385–412.
7. Askanazy M. Einiges zum Verständnis der Chlorome. Beitr Pathol Anat 1916; 63: 22–59.
8. Brennan D. Chloroma. The recent literature and a case report. Bull Johns Hopkins Hosp 1926; 3: 189–215.
9. Waldstein L. Ein Fall von progressiver Anämie und darauffolgender Leukocythemie mit Knochenmarkerkrankung und einem sogenannten Chlorom (Chlorolymphom). Virchows Arch Pathol Anat 1883; 91: 12.
10. Dock G, Warthin AS. A new case of chloroma with leukemia with a study of cases reported since 1893. Med News 1904; 85: 971.
11. Donner L, Středa A, Vaněk J. Chloroleukemie. Čas Lék Čes 1951; 90: 278–284.
12. Türk W. Akute myeloide Leukämie mit Grünfärbung des Knochenmarks. Mitt Gesellschft Innere Med Kinderhk 1903; 2: 39.
13. Butterfield EE. Beitrag zum Morphologie der Chloromzellen. Folia Haematol 1909; VIII: 179–184.
14. Naegeli O. Blutkrankheiten und Blutdiagnostik. 5. vyd. Berlin: Springer 1931.
15. Schultz J, Rosenthal S. Iron (II) inactivation of myeloperoxidase. J Biol Chem 1959; 234: 2486–2490.
16. Filip O, Bednár B. Chloroma and chloroleukemia. Neoplasma 1966; 13: 525–530.
17. Wiernik PH, Serpick AA. Granulocytic sarcoma (chloroma). Blood 1970; 35: 361–369.
18. Türk W. Vorlesungen über klinische Hämatologie. Wien: Braumüller 1904.
19. Netoušek M. Klinická hematologie. Praha: Státní zdravotnické nakladatelství 1962.
20. Ławkowicz W, Krzemińska-Ławkowicz I. Hematologický atlas. Směrnice pro rozpoznání nemocí krvetvorné soustavy. Praha: Státní zdravotnické nakladatelství 1953.
21. Risak E. Die Fibrinopenie. Z Klin Med 1935; 128: 605–629.
22. Croizat P, Favre-Gilly J. Les aspects du syndrome hémorragique des leucémies; a propos de 12 cas de thrombocytopénie et d‘un cas de fibrinopénie. Sang 1949; 20: 417–421.
23. Jones ME, Saleem A. Acute promyelocytic leukemia. A review of literature. Am J Med 1978; 65: 673–677.
24. Ross RR. Chloroma and chloroleukemia. Am J Med 1955; 18: 671–676.
25. Hillestad LK. Acute promyelocytic leukemia. Acta Med Scand 1957; 159: 189–194.
26. Stormorken H. Fibrinolytic purpura associated with myelogenous leukemia; case. Tidsskr Nor Lægeforen 1956; 76: 754.
27. Bernard J, Mathé G, Boulay J et al. La leucose aiguë à promyélocytes. Etude portant sur vingt observations. Schweiz Med Wochenschr 1959; 89: 604–608.
28. Rosenthal RL. Acute promyelocytic leukemia associated with hypofibrinogenemia. Blood 1963; 21: 495–508.
29. Bernard J, Lasneret J, Chome J et al. A cytological and histological study of aute premyelocytic leukaemia. J Clin Pathol 1963; 16: 319–324.
30. Baker WG, Bang NU, Nachman RL et al. Hypofibrinogenemic hemorrhage in acute myelogenous leukemia treated with heparin. With autopsy findings of widespread intravascular clotting. Ann Intern Med 1964; 61: 116–123.
31. Schwarz J, Lemez P, Lukasova M et al. High incidence of thromboembolic events in leukemic patients with acute promyelocytic leukemia (APL). Blood 1996; 88 (Suppl 1, Part 2): 169b. Abstract 3404.
32. Bernard J, Weil M, Boiron M et al. Acute promyelocytic leukemia: results of treatment by daunorubicin. Blood 1973; 41: 489–496.
33. Cunningham I, Gee TS, Reich LM et al. Acute promyelocytic leukemia: treatment results during a decade at Memorial Hospital. Blood 1989; 73: 1116–1122.
34. Sanz MA, Jarque I, Martín G et al. Acute promyelocytic leukemia. Therapy results and prognostic factors. Cancer 1988; 61: 7–13.
35. Bessis M, Breton-Gorius J. Pathologie et asychronisme de dévelopment des organelles cellulaires au cours des leucémies aiguës granulocytaires. Etude au microscope électronique. Nouv Rev Fr Hématol 1969; 9: 245–277.
36. Tan HK, Wages B, Gralnick HR. Ultrastructural studies in acute promyelocytic leukemia. Blood 1972; 39: 628–636.
37. Galton DAG, Dacie JV. Classification of acute leukaemias. Blood Cells 1975; 1: 17–24.
38. Bennett JM, Catovsky D, Daniel MT et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 1976; 33: 451–458.
39. Bennett JM, Catovsky D, Daniel MT et al. A variant form of hypergranular promyelocytic leukaemia (M3). Br J Haematol 1980; 44: 169–170.
40. Liso V, Troccoli G, Grande M. Cytochemical study of acute promyelocytic leukaemia. Blut 1975; 30: 261–268.
41. Das Gupta A, Sapre RS, Shah AS et al. Cytochemical and immunophenotypic heterogeneity in acute promyelocytic leukemia. Acta Haematol 1989; 81: 5–9.
42. Neame PB, Soamboonsrup P, Leber B et al. Morphology of acute promyelocytic leukemia with cytogenetic or molecular evidence for the diagnosis: characterization of additional microgranular variants. Am J Hematol 1997; 56: 131–142.
43. Sainty D, Liso V, Cantù-Rajnoldi A et al. A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements. Blood 2000; 96: 1287–1296.
44. Liso V, Bennett J. Morphological and cytochemical characteristics of leukaemic promyelocytes. Best Pract Res Clin Haematol 2003; 16: 349–355.
45. Rowley JD, Golomb HM, Dougherty C. 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet 1977; 1: 549–550.
46. Larson RA, Kondo K, Vardiman JW et al. Evidence for a 15;17 translocation in every patient with acute promyelocytic leukemia. Am J Med 1984; 76: 827–841.
47. Golomb HM, Rowley JD, Vardiman JW et al. “Microgranular” acute promyelocytic leukemia: a distinct clinical, ultrastructural, and cytogenetic entity. Blood 1980; 55: 253–259.
48. Petkovich M, Brand NJ, Krust A et al. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 1987; 330: 444–450.
49. Giguere V, Ong ES, Segui P et al. Identification of a receptor for the morphogen retinoic acid. Nature 1987; 330: 624–629.
50. Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J 1996; 10: 940–954.
51. Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988; 240: 889–895.
52. Umesono K, Giguere V, Glass CK et al. Retinoic acid and thyroid hormone induce gene expression through a common responsive element. Nature 1988; 336: 262–265.
53. de Thé H, Chomienne C, Lanotte M et al. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature 1990; 347: 558–561.
54. Chen SJ, Chen Z, Chen A et al. Occurrence of distinct PML‑RARα fusion gene isoforms in patients with acute promyelocytic leukemia detected by reverse transcriptase/polymerase chain reaction. Oncogene 1992; 7: 1223–1232.
55. Pandolfi PP, Alcalay M, Fagioli M et al. Genomic variability and alternative splicing generate multiple PML/RARα transcripts that encode aberrant PML proteins and PML/RARα isoforms in acute promyelocytic leukaemia. EMBO J 1992; 11: 1397–1407.
56. Diverio D, Riccioni R, Pistilli A et al. Improved rapid detection of the PML/RARα fusion gene in acute promyelocytic leukemia. Leukemia 1996; 10: 1214–1216.
57. Gallagher RE, Willman CL, Slack JL et al. Association of PML‑RARα fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia: an Intergroup molecular study. Blood 1997; 90: 1656–1663.
58. Slack JL, Willman CL, Andersen JW et al. Molecular analysis and clinical outcome of adult APL patients with the type V PML‑RARα isoform: results from Intergroup protocol 0129. Blood 2000; 95: 398–403.
59. O‘Connor SJ, Evans PA, Morgan GJ. Diagnostic approaches to acute promyelocytic leukaemia. Leuk Lymphoma 1999; 33: 53–63.
60. Grimwade D, Howe K, Langabeer S et al. Establishing the presence of the t(15;17) in suspected acute promyelocytic leukaemia: cytogenetic, molecular and PML immunofluorescence assessment of patients entered into the M.R.C. ATRA trial. Br J Haematol 1996; 94: 557–573.
61. Grimwade D, Biondi A, Mozziconacci MJ et al. Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Blood 2000; 96: 1297–1308.
62. Borrow J, Solomon E. Molecular analysis of the t(15;17) translocation in acute promyelocytic leukaemia. Baillière’s Clin Haematol 1992; 5: 833–856.
63. Frankel SR. Acute promyelocytic leukemia. New insights into diagnosis and therapy. Hematol Oncol Clin North Am 1993; 7: 109–138.
64. Mancini M, Nanni M, Cedrone M et al. Combined cytogenetic, FISH and molecular analysis in acute promyelocytic leukaemia at diagnosis and in complete remission. Br J Haematol 1995; 91: 878–884.
65. Miller WH Jr, Kakizuka A, Frankel SR et al. Reverse transcription polymerase chain reaction for the rearranged retinoic acid receptor alpha clarifies diagnosis and detects minimal residual disease in acute promyelocytic leukemia. Proc Natl Acad Sci USA 1992; 89: 2694–2698.
66. Cassinat B, Zassadowski F, Balitrand N et al. Quantitation of minimal residual disease in acute promyelocytic leukemia patients with t(15;17) translocation using real-time RT‑PCR. Leukemia 2000; 14: 324–328.
67. Mandelli F, Diverio D, Avvisati G et al. Molecular remission in PML/RARα-positive acute promyelocytic leukemia by combined all‑trans retinoic acid and idarubicin (AIDA) therapy. Blood 1997; 90: 1014–1021.
68. Polák J, Marková J, Schwarz J et al. Užití kvantitativního stanovení exprese genu Wilmsova tumoru 1 pro monitorování reziduální nemoci pacientů s akutní myeloidní leukemií. Čas Lék Čes 2006; 145: 36–42.
69. Brunning RD, Bennett J, Matutes E et al. Acute myeloid leukaemia with recurrent genetic abnormalities. In: Jaffe ES, Harris NL, Stein H et al (eds).World Health Organization classification of tumours. Pathology and genetics. Tumours of haematopoietic and lymphoid tissues. Lyon: IARC 2001: 81–87.
70. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002; 100: 2292–2302.
71. Cinátl J, Paluska E, Chudomel V et al. Culture of macrophage cell lines from normal mouse bone marrow. Nature 1982; 298: 388–389.
72. Nowell PC. Differentiation of human leukemic leukocytes in tissue culture. Exp Cell Res 1960; 19: 267–277.
73. Pluznik DH, Sachs L. The cloning of normal “mast” cells in tissue culture. J Cell Physiol 1965; 66: 319–324.
74. Pluznik DH, Sachs L. The induction of clones of normal mast cells by a substance from conditioned medium. Exp Cell Res 1966; 43: 553–563.
75. Bradley TR, Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci 1966; 44: 287–299.
76. Paran M, Sachs L, Barak Y et al. In vitro induction of granulocyte differentiation in hematopoietic cells from leukemic and non-leukemic patients. Proc Natl Acad Sci USA 1970; 67: 1542–1549.
77. Friend C, Scher W, Holland JG et al. Hemoglobin synthesis in murine virus‑induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci USA 1971; 68: 378–382.
78. Lotem J, Sachs L. Different blocks in the differentiation of myeloid leukemic cells. Proc Natl Acad Sci USA 1974; 71: 3507–3511.
79. Metcalf D. Humoral regulators in the development and progression of leukemia. Adv Cancer Res 1971; 14: 181–230.
80. Lotem J, Sachs L. Independent regulation of myeloid cell growth and differentiation inducing proteins: in vivo regulation by compounds that induce inflammation. Int J Cancer 1985; 35: 93–100.
81. Sachs L, Lotem J, Shabo Y. The molecular regulators of macrophage and granulocyte development. Role of MGI-2/IL‑6. Ann N Y Acad Sci 1989; 557: 417–435.
82. Gunz FW, Vincent PC. Towards a cure of acute granulocytic leukemia? Leuk Res 1977; 1: 51–66.
83. Sachs L. The differentiation of myeloid leukaemia cells: new possibilities for therapy. Br J Haematol 1978; 40: 509–517.
84. Collins SJ, Gallo RC, Gallagher RE. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature 1977; 270: 347–349.
85. Minowada J. Immunology of leukemic cells. In: Gunz W, Henderson ES (eds). Leukemia. 1st ed. New York: Grune and Stratton 1978: 119–139.
86. Dalton WT Jr, Ahearn MJ, McCredie KB et al. HL‑60 cell line was derived from a patient with FAB-M2 and not FAB-M3. Blood 1988; 71: 242–247.
87. Collins SJ, Ruscetti FW, Gallagher RE et al. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci USA 1978; 75: 2458–2462.
88. Breitman TR, Selonick SE, Collins SJ. Induction of differentiation of the human promyelocytic leukemia cell line (HL‑60) by retinoic acid. Proc Natl Acad Sci USA 1980; 77: 2936–2940.
89. Honma Y, Takenaga K, Kasukabe T et al. Induction of differentiation of cultured human promyelocytic leukemia cells by retinoids. Biochem Biophys Res Commun 1980; 95: 507–512.
90. Breitman TR, Collins SJ, Keene BR. Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid. Blood 1981; 57: 1000–1004.
91. Muindi JR, Frankel SR, Huselton C et al. Clinical pharmacology of oral all‑trans retinoic acid in patients with acute promyelocytic leukemia. Cancer Res 1992; 52: 2138–2142.
92. Stöckbauer P, Gahmberg CG, Andersson LC. Changes in cell surface glycoproteins and antigens during differentiation of the human myeloid leukemia cell lines ML‑1, ML‑2, and HL‑60. Cancer Res 1985; 45: 2821–2826.
93. Schwarz J, Stöckbauer P, Soucek J et al. Features of immaturity in cells derived from granulocytic differentiation inducer treated human myeloid leukaemia (ML‑1) cells. Leuk Res 1987; 11: 869–876.
94. Warrell RP Jr, Frankel SR, Miller WH Jr et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all‑trans‑retinoic acid). N Engl J Med 1991; 324: 1385–1393.
95. Flynn PJ, Miller WJ, Weisdorf DJ et al. Retinoic acid treatment of acute promyelocytic leukemia: in vitro and in vivo observations. Blood 1983; 62: 1211–1217.
96. Daenen S, Vellenga E, van Dobbenburgh OA et al. Retinoic acid as antileukemic therapy in a patient with acute promyelocytic leukemia and Aspergillus pneumonia. Blood 1986; 67: 559–561.
97. Wolf G. A history of vitamin A and retinoids. FASEB J 1996; 10: 1102–1107.
98. Smith MA, Parkinson DR, Cheson BD et al. Retinoids in cancer therapy. J Clin Oncol 1992; 10: 839–864.
99. Lippman SM, Kessler JF, Meyskens FL Jr Retinoids as preventive and therapeutic anticancer agents (Part I). Cancer Treat Rep 1987; 71: 391–405.
100. Lippman SM, Kessler JF, Meyskens FL Jr. Retinoids as preventive and therapeutic anticancer agents (Part II). Cancer Treat Rep 1987; 71: 493–515.
101. Pokorný M, Pavcová Š, Voltr J. Retinoidy a jejich použití v dermatologii. Prakt Lék 1983; 63: 685–686.
102. Warrell RP Jr. Applications for retinoids in cancer therapy. Semin Hematol 1994; 31: 1–13.
103. Huang ME, Ye YC, Chen SR et al. Use of all‑trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988; 72: 567–572.
104. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008; 111: 2505–2515.
105. Degos L. Introduction to the round table on retinoids and differentiation therapy. Nouv Rev Fr Hématol 1990; 32: 25–26.
106. Visani G, Manfroi S, Tosi P et al. All‑trans‑retinoic acid and pseudotumor cerebri. Leuk Lymphoma 1996; 23: 437–442.
107. Chomienne C, Ballerini P, Balitrand N et al. Retinoic acid therapy for promyelocytic leukaemia. Lancet 1989; 2: 746–747.
108. Degos L, Chomienne C, Daniel MT et al. Treatment of first relapse in acute promyelocytic leukaemia with all‑trans retinoic acid. Lancet 1990; 336: 1440–1441.
109. Degos L. The history of acute promyelocytic leukaemia. Br J Haematol 2003; 122: 539–553.
110. Smith MA, Adamson PC, Balis FM et al. Phase I and pharmacokinetic evaluation of all‑trans‑retinoic acid in pediatric patients with cancer. J Clin Oncol 1992; 10: 1666–1673.
111. Adamson PC, Bailey J, Pluda J et al. Pharmacokinetics of all‑trans‑retinoic acid administered on an intermittent schedule. J Clin Oncol 1995; 13: 1238–1241.
112. Adamson PC. Pharmacokinetics of all‑trans‑retinoic acid: clinical implications in acute promyelocytic leukemia. Semin Hematol 1994; 31: 14–17.
113. Ohashi H, Ichikawa A, Takagi N et al. Remission induction of acute promyelocytic leukemia by all‑trans‑retinoic acid: molecular evidence of restoration of normal hematopoiesis after differentiation and subsequent extinction of leukemic clone. Leukemia 1992; 6: 859–862.
114. Elliott S, Taylor K, White S et al. Proof of differentiative mode of action of all‑trans retinoic acid in acute promyelocytic leukemia using X‑linked clonal analysis. Blood 1992; 79: 1916–1919.
115. Chen SJ, Zhu YJ, Tong JH et al. Rearrangements in the second intron of the RARA gene are present in a large majority of patients with acute promyelocytic leu-kemia and are used as molecular marker for retinoic acid‑induced leukemic cell differentiation. Blood 1991; 78: 2696–2701.
116. Fenaux P, Le Deley MC, Castaigne S et al. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. Blood 1993; 82: 3241–3249.
117. Sanz MA, Martín G, Rayón C et al. A modified AIDA protocol with an-thracycline‑based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARα-positive acute promyelocytic leukemia. PETHEMA group. Blood 1999; 94: 3015–3021.
118. Miller WH Jr, Jakubowski A, Tong WP et al. 9-cis retinoic acid induces complete remission but does not reverse clinically acquired retinoid resistance in acute promyelocytic leukemia. Blood 1995; 85: 3021–3027.
119. Soignet SL, Benedetti F, Fleischauer A et al. Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia. Leukemia 1998; 12: 1518–1521.
120. Chen SJ, Zelent A, Tong JH et al. Rearrangements of the retinoic acid receptor alpha and promyelocytic leukemia zinc finger genes resulting from t(11;17)(q23;q21) in a patient with acute promyelocytic leukemia. J Clin Invest 1993; 91: 2260–2267.
121. Chen GQ, Shi XG, Tang W et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose‑dependent dual effects on APL cells. Blood 1997; 89: 3345–3353.
122. Shen ZX, Chen GQ, Ni JH et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997; 89: 3354–3360.
Labels
Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
![Issue 7-8](https://www.prolekare.cz/media/cache/resolve/journal_issue/media/image_pdf/b4c723170d6c420fa274e0cf25a71cb9.jpeg)
2008 Issue 7-8
Most read in this issue
- An urgency in hematology: acute promyelocytic leukemia – principles of diagnosis
- Coagulopathy and differentiation syndrome: the main complications of the initial treatment of acute promyelocytic leukemia
- Brief case reports illustrate various initial courses in acute promyelocytic leukemia
- Leukemogenesis and therapy of acute promyelocytic leukemia: from the worse to the most favorable subtype of acute myeloid leukemia