Advertisement

Pathologie pp 115-139 | Cite as

Neoplastische Bildungsstörungen der Hämatopoiese mit Ausreifungsverlust

  • Hans H. KreipeEmail author
Chapter

Zusammenfassung

Die neoplastischen Bildungsstörungen der Hämatopoese mit Ausreifungsverlust umfassen die große und heterogene Gruppe der akuten myeloischen Leukämien. Die gegenwärtige WHO Klassifikation stellt einen Hybrid aus morphologischen und molekularen Definitionsmerkmalen dar. Neben dem Phänotyp und der zugrundeliegenden genetischen Aberration kommen als Klassifikationsprinzip auch weitere Patientenmerkmale hinzu, die Verlauf und Prognose mitbestimmen: Genetische Prädisposition (z.B. Down Syndrom, Fanconi Anämie u.a.), vorbestehende klonale Proliferationen wie MDS oder myelodysplastische/myeloproliferative Neoplasien und eine vorangegangene Chemotherapie. Damit ergibt sich für die Diagnostik ein komplexes Bild aus subtilen morphologischen, immunhistochemischen und vielfältigen, nur partiell mit einem morphologischen Korrelat versehenen, molekulargenetischen Klassifikationsmerkmalen, die in diesem Kapitel in allen Facetten, ausgehend von den zytologischen und histologischen Befunden am Knochenmark, unter Einschluss neudefinierter hämatopoetischer Stammzell- und Vorläuferzellneoplasien dargestellt werden. Eine wichtige Aufgabe ist auch die Remissionsbeurteilung unter Therapie, die ebenfalls behandelt wird.

Literatur

  1. 1.
    Abdel-Wahab O, Levine RL (2013) Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood 121:3563–3572PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Abdou SM, Jadayel DM, Min T, Swansbury GJ, Dainton MG, Jafer O, Powles RL, Catovsky D (2002) Incidence of MLL rearrangement in acute myeloid leukemia, and a CALM-AF10 fusion in M4 type acute myeloblastic leukemia. Leuk Lymphoma 43:89–95PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Allen C, Hills RK, Lamb K et al (2013) The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia. Leukemia 27:1891–1901PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Alsabeh R, Brynes RK, Slovak ML, Arber DA (1997) Acute myeloid leukemia with t(6;9) (p23;q34): association with myelodysplasia, basophilia, and initial CD34 negative immunophenotype. Am J Clin Pathol 107:430–437PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Arber DA, Brunning RD, Le Beau MM, Falini B, Vardiman JW, Porwit A, Thiele J, Bloomfield CD (2008) Acute myeloid leukemia with recurrent genetic abnormalities. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (Hrsg) WHO Classification of haematopoietic and lymphoid tissues. IARC Press, Lyon, S 110–123Google Scholar
  6. 6.
    Arber DA, Brunning RD, Orazi A, Bain BJ, Porwit A, Vardiman JW, Le Beau MM, Greenberg PL (2008) Acute myeloid leukemia with myelodysplastic related changes. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (Hrsg) WHO Classification of haematopoietic and lymphoid tissues. IARC Press, Lyon, S 124–129Google Scholar
  7. 7.
    Arber DA, Brunning RD, Orazi A, Porwit A, Peterson L, Thiele J, Le Beau MM (2008) Acute myeloid leukemia not otherwise specified. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (Hrsg) WHO Classification of haematopoietic and lymphoid tissues. IARC Press, Lyon, S 130–139Google Scholar
  8. 8.
    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405CrossRefGoogle Scholar
  9. 9.
    Arbuthnot C, Wilde JT (2006) Haemostatic problems in acute promyelocytic leukaemia. Blood Rev 20:289–297PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Arnould C, Philippe C, Bourdon V, Gr goire MJ, Berger R, Jonveaux P (1999) The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia. Hum Mol Genet 8:1741–1749PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Bacher U, Haferlach C, Kern W, Haferlach T, Schnittger S (2008) Prognostic relevance of FLT3-TKD mutations in AML: the combination matters – an analysis of 3082 patients. Blood 111:2527–2537PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Bacher U, Schnittger S, Macijewski K et al (2012) Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity. Blood 119:4719–4722PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Bain BJ, Gilliland G, Horny H-P, Vardiman JW (2008) Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (Hrsg) WHO Classification of haematopoietic and lymphoid tissues. IARC Press, Lyon, S 68–73Google Scholar
  14. 14.
    Ball ED, Davis RB, Griffin JD, Mayer RJ, Davey FR, Arthur DC, Wurster-Hill D, Noll W, Elghetany MT, Allen SL et al (1991) Prognostic value of lymphocyte surface markers in acute myeloid leukemia. Blood 77:2242–2250PubMedPubMedCentralGoogle Scholar
  15. 15.
    Becher R, Haas OA, Graeven U, Bettelheim P, Ambros P, Fridrik M, Schaefer UW, Schmidt CG (1988) Translocation t(8;16) in acute monocytic leukemia. Cancer Genet Cytogenet 34:265–271PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Béné MC, Bernier M, Casasnovas RO, Castoldi G, Doekharan D, van der Holt B, Knapp W, Lemez P, Ludwig WD, Matutes E, Orfao A, Schoch C, Sperling C, van’t Veer MB MB (2001) Acute myeloid leukaemia M0: haematological, immunophenotypic and cytogenetic characteristics and their prognostic significance: an analysis in 241 patients. Br J Haematol 113:737–745PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Béné MC, Nebe T, Bettelheim P et al (2011) Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10. Leukemia 25:567–574PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Bhatia S (2013) Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol 40:666–675PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Borowitz MJ, Béné MC, Harris NL, Porwit A, Matutes E (2008) Acute leukemias with ambiguous lineage. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (Hrsg) WHO Classification of haematopoietic and lymphoid tissues. IARC Press, Lyon, S 150–154Google Scholar
  20. 20.
    Bowen D, Groves MJ, Burnett AK et al (2009) TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis. Leukemia 23:203–206PubMedCrossRefGoogle Scholar
  21. 21.
    Bradstock KF (1993) The diagnostic and prognostic value of immunophenotyping in acute leukemia. Pathology 25:367–374PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Breccia M, Mandelli F, Petti MC, D’Andrea M, Pescarmona E, Pileri SA, Carmosino I, Russo E, De Fabritiis P, Alimena G (2004) Clinico-pathological characteristics of myeloid sarcoma at diagnosis and during follow-up: report of 12 cases from a single institution. Leuk Res 28:1165–1169PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Brunning RD (2003) Classification of acute leukemias. Semin Diagn Pathol 20:142–153PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Burnett AK, Russell NH, Hills RK, United Kingdom National Cancer Research Institute Acute Myeloid Leukemia Study Group (2016) Higher daunorubicin exposure benefits FLT3 mutated acute myeloid leukemia. Blood 128:449–452PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Burroughs L, Woolfrey A, Shimamura A (2009) Shwachman-Diamond syndrome: a review of the clinical presentation, molecular pathogenesis, diagnosis, and treatment. Hematol Oncol Clin North Am 23:233–248PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Caligiuri MA, Strout MP, Lawrence D, Arthur DC, Baer MR, Yu F, Knuutila S, Mrózek K, Oberkircher AR, Marcucci G, de la Chapelle A, Elonen E, Block AW, Rao PN, Herzig GP, Powell BL, Ruutu T, Schiffer CA, Bloomfield CD (1998) Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics. Cancer Res 58:55–59PubMedPubMedCentralGoogle Scholar
  27. 27.
    Cancer Genome Atlas Research Network (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 368:2059–2074CrossRefGoogle Scholar
  28. 28.
    Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S, Zelent A (1993) Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J 12:1161–1167PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Chi Y, Lindgren V, Quigley S, Gaitonde S (2008) Acute myelogenous leukemia with t(6;9)(p23;q34) and marrow basophilia: an overview. Arch Pathol Lab Med 132:1835–1837PubMedPubMedCentralGoogle Scholar
  30. 30.
    Churpek JE, Godley LA (2016) How I diagnose and manage individuals at risk for inherited myeloid malignancies. Blood 128:1800–1813CrossRefGoogle Scholar
  31. 31.
    Churpek JE, Larson RA (2013) The evolving challenge of therapy-related myeloid neoplasms. Best Pract Res Clin Haematol 26:309–317PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Churpek JE, Pyrtel K, Kanchi KL et al (2015) Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia. Blood 126:2484–2490PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Cleven AH, Nardi V, Ok CY et al (2015) High p53 protein expression in therapy-related myeloid neoplasms is associated with adverse karyotype and poor outcome. Mod Pathol 28:552–563PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC, Majeti R (2014) Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci Usa 111:2548–2553PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Czader M, Orazi A (2009) Therapy-related myeloid neoplasms. Am J Clin Pathol 132:410–425PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Devillier R, Mansat-De Mas V, Gelsi-Boyer V et al (2015) Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes. Oncotarget 6:8388–8396PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Löwenberg B, Bloomfield CD (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129:424–447PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Döhner H, Weisdorf DJ, Bloomfield CD (2015) Acute leukemia. N Engl J Med 372:1136–1152CrossRefGoogle Scholar
  39. 39.
    Duchayne E, Fenneteau O, Pages MP, Sainty D, Arnoulet C, Dastugue N, Garand R, Flandrin G, Groupe Français d’Hématologie Cellulaire, Groupe Français de Cytogénétique Hématologique (2003) Acute megakaryoblastic leukaemia: a national clinical and biological study of 53 adult and childhood cases by the Groupe Français d’Hématologie Cellulaire (GFHC). Leuk Lymphoma 44:49–58PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Dufour A, Schneider F, Metzeler KH et al (2010) Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol 28:570–577PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Duployez N, Marceau-Renaut A, Boissel N et al (2016) Comprehensive mutational profiling of core binding factor acute myeloid leukemia. Blood 127:2451–2459PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Faber ZJ, Chen X, Gedman AL et al (2016) The genomic landscape of core-binding factor acute myeloid leukemias. Nat Genet 48:1551–1556PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Facchetti F, Jones DM, Petrella T (2008) Blastic plasmocytoid dendritic cell neoplasm. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (Hrsg) WHO Classification of haematopoietic and lymphoid tissues. IARC Press, Lyon, S 145–147Google Scholar
  44. 44.
    Falini B, Macijewski K, Weiss T et al (2010) Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1). Blood 115:3776–3786PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, La Starza R, Diverio D, Colombo E, Santucci A, Bigerna B, Pacini R, Pucciarini A, Liso A, Vignetti M, Fazi P, Meani N, Pettirossi V, Saglio G, Mandelli F, Lo-Coco F, Pelicci PG, Martelli MF, GIMEMA Acute Leukemia Working Party (2005) Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 352:254–266PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Foley R, Soamboonsrup P, Carter RF, Benger A, Meyer R, Walker I, Wan Y, Patterson W, Orzel A, Sunisloe L, Leber B, Neame PB (2001) CD34-positive acute promyelocytic leukemia is associated with leukocytosis, microgranular/hypogranular morphology, expression of CD2 and bcr3 isoform. Am J Hematol 67:34–41PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Gaidzik V, Döhner K (2008) Prognostic implications of gene mutations in acute myeloid leukemia with normal cytogenetics. Semin Oncol 35:346–355PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Gaidzik VI, Bullinger L, Schlenk RF et al (2011) RUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study group. J Clin Oncol 29:1364–1372PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Gaidzik VI, Teleanu V, Papaemmanuil E et al (2016) RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features. Leukemia 30:2160–2168PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Medical Research Council Adult Leukaemia Working Party, Gale RE, Green C, Allen C et al (2008) The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 111:2776–2784CrossRefGoogle Scholar
  51. 51.
    Godley LA (2014) Inherited predisposition to acute myeloid leukemia. Semin Hematol 51:306–321PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Gough SM, Slape CI, Aplan PD (2011) NUP98 gene fusions and hematopoietic malignancies: common themes and new biologic insights. Blood 118:6247–6257PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Green CL, Koo KK, Hills RK, Burnett AK, Linch DC, Gale RE (2010) Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. J Clin Oncol 28:2739–2747PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    National Cancer Research Institute Adult leukaemia Working Group, Grimwade D, Hills RK, Moorman AV et al (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116:354–365CrossRefGoogle Scholar
  55. 55.
    Grimwade D, Ivey A, Huntly BJ (2016) Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood 127:29–41PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Gröschel S, Sanders MA, Hoogenboezem R et al (2014) A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell 157:369–381PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Gruber TA, Larson Gedman A, Zhang J et al (2012) An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia. Cancer Cell 22:683–697PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Haferlach C, Dicker F, Herholz H, Schnittger S, Kern W, Haferlach T (2008) Mutations of the TP53 gene in acute myeloid leukemia are strongly associated with a complex aberrant karyotype. Leukemia 22:1539–1541PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Haferlach C, Mecucci C, Schnittger S et al (2009) AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood 114:3024–3032PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Haferlach T, Bacher U, Kern W, Schnittger S, Haferlach C (2007) Diagnostic pathways in acute leukemias: a proposal for a multimodal approach. Ann Hematol 86:311–327PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Haferlach T, Kohlmann A, Klein HU, Ruckert C, Dugas M, Williams PM, Kern W, Schnittger S, Bacher U, Löffler H, Haferlach C (2009) AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features. Leukemia 23:934–943PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Haferlach T, Stengel A, Eckstein S et al (2016) The new provisional WHO entity „RUNX1 mutated AML“ shows specific genetics but no prognostic influence of dysplasia. Leukemia 30:2109–2112PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Harris AC, Todd WM, Hackney MH, Ben-Ezra J (1994) Bone marrow changes associated with recombinant granulocyte-macrophage and granulocyte colony-stimulating factors. Discrimination of granulocytic regeneration. Arch Pathol Lab Med 118:624–629PubMedPubMedCentralGoogle Scholar
  64. 64.
    Harutyunyan AS, Giambruno R, Krendl C et al (2016) Germline RBBP6 mutations in familial n myeloproliferative neoplasms. Blood 127:362–365PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Heim S, Avanzi GC, Billström R, Kristoffersson U, Mandahl N, Bekassy AN, Garwicz S, Wiebe T, Pegoraro L, Falda M et al (1987) A new specific chromosomal rearrangement, t(8;16) (p11;p13), in acute monocytic leukaemia. Br J Haematol 66:323–326PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Hollink IH, van den Heuvel-Eibrink MM, Arentsen-Peters ST et al (2011) NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern. Blood 118:3645–3656PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Hulegardh E, Nilsson C, Lazarevic V et al (2015) Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish Acute Leukemia Registry. Am J Hematol 90:208–214PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Hurwitz CA, Raimondi SC, Head D, Krance R, Mirro J Jr, Kalwinsky DK, Ayers GD, Behm FG (1992) Distinctive immunophenotypic features of t(8;21)(q22;q22) acute myeloblastic leukemia in children. Blood 80:3182–3188PubMedPubMedCentralGoogle Scholar
  69. 69.
    Innes DJ Jr, Hess CE, Bertholf MF, Wade P (1987) Promyelocyte morphology. Differentiation of acute promyelocytic leukemia from benign myeloid proliferations. Am J Clin Pathol 88:725–729PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Kaleem Z, White G (2001) Diagnostic criteria for minimally differentiated acute myeloid leukemia (AML-M0). Evaluation and a proposal. Am J Clin Pathol 115:876–884PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Kayser S, Döhner K, Krauter J, al German-Austrian AMLSG (2011) The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood 117:2137–2145PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Khalidi HS, Medeiros LJ, Chang KL, Brynes RK, Slovak ML, Arber DA (1998) The immunophenotype of adult acute myeloid leukemia: high frequency of lymphoid antigen expression and comparison of immunophenotype, French-American-British classification, and karyotypic abnormalities. Am J Clin Pathol 109:211–220PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Khoury H, Dalal BI, Nevill TJ, Horsman DE, Barnett MJ, Shepherd JD, Toze CL, Conneally EA, Sutherland HJ, Hogge DE, Nantel SH (2003) Acute myelogenous leukemia with t(8;21) – identification of a specific immunophenotype. Leuk Lymphoma 44:1713–1718PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Konoplev S, Huang X, Drabkin HA, Koeppen H, Jones D, Kantarjian HM, Garcia-Manero G, Chen W, Medeiros LJ, Bueso-Ramos CE (2009) Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis. Cancer 115:4737–4744PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Kozlov I, Beason K, Yu C, Hughson M (2005) CD79a expression in acute myeloid leukemia t(8;21) and the importance of cytogenetics in the diagnosis of leukemias with immunophenotypic ambiguity. Cancer Genet Cytogenet 163:62–67PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Krasinskas AM, Wasik MA, Kamoun M, Schretzenmair R, Moore J, Salhany KE (1998) The usefulness of CD64, other monocyte-associated antigens, and CD45 gating in the subclassification of acute myeloid leukemias with monocytic differentiation. Am J Clin Pathol 110:797–805PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Le Deley MC, Suzan F, Cutuli B, Delaloge S, Shamsaldin A, Linassier C, Clisant S, de Vathaire F, Fenaux P, Hill C (2007) Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol 25:292–300PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Lee JJ, Cho D, Chung IJ, Cho SH, Park KS, Park MR, Ryang DW, Kim HJ (2003) CD34 expression is associated with poor clinical outcome in patients with acute promyelocytic leukemia. Am J Hematol 73:149–153PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Leu L, Mohassel L (2009) Arsenic trioxide as first-line treatment for acute promyelocytic leukemia. Am J Health Syst Pharm 66:1913–1918PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Linch DC, Hills RK, Burnett AK, Khwaja A, Gale RE (2014) Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia. Blood 124:273–276PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Lindsley RC, Mar BG, Mazzola E et al (2015) Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 125:1367–1376PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Lock RJ, Virgo PF, Kitchen C, Evely RS (2004) Rapid diagnosis and characterization of acute promyelocytic leukaemia in routine laboratory practice. Clin Lab Haematol 26:101–106PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Löffler H, Rastetter J, Haferlach T (2004) Atlas der klinischen Hämatologie. Springer, BerlinCrossRefGoogle Scholar
  84. 84.
    Marcucci G, Haferlach T, Döhner H (2011) Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol 29:475–486PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Martinelli G, Ottaviani E, Buonamici S, Isidori A, Borsaru G, Visani G, Piccaluga PP, Malagola M, Testoni N, Rondoni M, Nucifora G, Tura S, Baccarani M (2003) Association of 3q21q26 syndrome with different RPN1/EVI1 fusion transcripts. Haematologica 88:1221–1228PubMedPubMedCentralGoogle Scholar
  86. 86.
    Mendler JH, Maharry K, Radmacher MD et al (2012) RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and microRNA expression signatures. J Clin Oncol 30:3109–3118PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Metzeler KH, Becker H, Maharry K et al (2011) ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood 118:6920–6929PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    AMLCG Study Group, Metzeler KH, Herold T, Rothenberg-Thurley M et al (2016) AMLCG Study Group. Spectr Progn Relev Driv Gene Mutat Acute Myeloid Leuk Blood 128:686–698Google Scholar
  89. 89.
    Micol JB, Duployez N, Boissel N et al (2014) Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations. Blood 124:1445–1449PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Moorman AV, Hagemeijer A, Charrin C, Rieder H, Secker-Walker LM (1998) The translocations, t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic and clinical profile of 53 patients. European 11q23 Workshop participants. Leukemia 12:805–810PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Mrózek K, Bloomfield CD (2008) Clinical significance of the most common chromosome translocations in adult acute myeloid leukemia. J Natl Cancer Inst Monogr 39:52–57CrossRefGoogle Scholar
  92. 92.
    Mueller BU, Pabst T, Fos J, Petkovic V, Fey MF, Asou N, Buergi U, Tenen DG (2006) ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression. Blood 107:3330–3338PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Nacheva EP, Grace CD, Brazma D et al (2013) Does BCR/ABL1 positive acute myeloid leukaemia exist? Br J Haematol 161:541–550PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Nakamura H, Kuriyama K, Sadamori N, Mine M, Itoyama T, Sasagawa I, Matsumoto K, Tsuji Y, Asou N, Kageyama SI, Sakamaki H, Emi N, Ohno R, Tomonaga M (1997) Morphological subtyping of acute myeloid leukemia with maturation (AML-M2): homogeneous pink-colored cytoplasm of mature neutrophils is most characteristic of AML-M2 with t(8;21). Leukemia 11:651–655PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Ngo N, Lampert IA, Naresh KN (2008) Bone marrow trephine findings in acute myeloid leukaemia with multilineage dysplasia. Br J Haematol 140:279–286PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Oki Y, Kantarjian HM, Zhou X, Cortes J, Faderl S, Verstovsek S, O’Brien S, Koller C, Beran M, Bekele BN, Pierce S, Thomas D, Ravandi F, Wierda WG, Giles F, Ferrajoli A, Jabbour E, Keating MJ, Bueso-Ramos CE, Estey E, Garcia-Manero G (2006) Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center. Blood 107:880–884PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Orazi A, O’Malley DP, Jiang J, Vance GH, Thomas J, Czader M, Fang W, An C, Banks PM (2005) Acute panmyelosis with myelofibrosis: an entity distinct from acute megakaryoblastic leukemia. Mod Pathol 18:603–614PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Pabst T, Eyholzer M, Fos J, Mueller BU (2009) Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis. Br J Cancer 100:1343–1346PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Papaemmanuil E, Gerstung M, Bullinger L et al (2016) Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 374:2209–2221PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Paschka P, Du J, Schlenk RF et al (2013) Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG). Blood 121:170–177PubMedCrossRefGoogle Scholar
  101. 101.
    Paschka P, Schlenk RF, Gaidzik VI et al (2015) ASXL1 mutations in younger adult patients with acute myeloid leukemia: a study by the German-Austrian Acute Myeloid Leukemia Study Group. Haematologica 100:324–330PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Paschka P (2008) Core binding factor acute myeloid leukemia. Semin Oncol 35:410–417PubMedCrossRefGoogle Scholar
  103. 103.
    Pearson MG, Vardiman JW, Le Beau MM, Rowley JD, Schwartz S, Kerman SL, Cohen MM, Fleischman EW, Prigogina EL (1985) Increased numbers of marrow basophils may be associated with a t(6;9) in ANLL. Am J Hematol 18:393–403PubMedCrossRefGoogle Scholar
  104. 104.
    Peterson L, Bloomfield CD, Döhner H, Niemeyer C, Godley L (2016) Myeloid neoplasms with germline predisposition. In: Swerdlow S, Campo E, Harris NL et al (Hrsg) World health organization classification of tumours of haematopoietic and lymphoid tissues, 4. Aufl. World Health Organization, LyonGoogle Scholar
  105. 105.
    Peterson LC, Parkin JL, Arthur DC, Brunning RD (1991) Acute basophilic leukemia. A clinical, morphologic, and cytogenetic study of eight cases. Am J Clin Pathol 96:160–170PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Pileri SA, Orazi A, Falini B (2008) Myeloid sarcoma. In: Swerdlow S, Campo E, Harris NL et al (Hrsg) World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. World Health Organization, Lyon, S 140–141Google Scholar
  107. 107.
    Pratcorona M, Abbas S, Sanders MA et al (2012) Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value. Haematologica 97:388–392PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ (1996) The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood 87:882–886PubMedGoogle Scholar
  109. 109.
    Rizzatti EG, Garcia AB, Portieres FL, Silva DE, Martins SL, Falcão RP (2002) Expression of CD117 and CD11b in bone marrow can differentiate acute promyelocytic leukemia from recovering benign myeloid proliferation. Am J Clin Pathol 118:31–37PubMedCrossRefGoogle Scholar
  110. 110.
    Rosenthal NS, Farhi DC (1991) Dysmegakaryopoiesis resembling acute megakaryoblastic leukemia in treated acute myeloid leukemia. Am J Clin Pathol 95:556–560PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Rücker FG, Schlenk RF, Bullinger L et al (2012) TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood 119:2114–2121PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Sanz MA, Grimwade D, Tallman MS et al (2009) Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 113:1875–1891PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H, German-Austrian Acute Myeloid Leukemia Study Group (2008) Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 358:1909–1918PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    German-Austrian AML Study Group, Schlenk RF, Kayser S, Bullinger L et al (2014) Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood 124:3441–3449CrossRefGoogle Scholar
  115. 115.
    Schoch C, Schnittger S, Klaus M, Kern W, Hiddemann W, Haferlach T (2003) AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. Blood 102:2395–2402PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Shih AH, Chung SS, Dolezal EK et al (2013) Mutational analysis of therapy-related myelodysplastic syndromes and acute myelogenous leukemia. Haematologica 98:908–912PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Stein E, McMahon B, Kwaan H, Altman JK, Frankfurt O, Tallman MS (2009) The coagulopathy of acute promyelocytic leukaemia revisited. Best Pract Res Clin Haematol 22:153–163PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Stirewalt DL, Radich JP (2003) The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer 3:650–665PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Tallman MS, Altman JK (2009) How I treat acute promyelocytic leukemia. Blood 114:5126–5135PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    Tang JL, Hou HA, Chen CY et al (2009) AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations. Blood 114:5352–5361PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Taskesen E, Bullinger L, Corbacioglu A et al (2011) Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood 117:2469–2475PubMedCrossRefGoogle Scholar
  122. 122.
    Cancer Genome Atlas Research Network (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 368:2059–2074CrossRefGoogle Scholar
  123. 123.
    Thol F, Kölking B, Hollink IH et al (2013) Analysis of NUP98/NSD1 translocations in adult AML and MDS patients. Leukemia 27:750–754PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Vardiman JW, Arber DA, Brunning RD, Larson RA, Matutes E, Baumann I, Thiele J (2008) Therapy-related myeloid neoplasms. In: Swerdlow S, Campo E, Harris NL et al (Hrsg) World health organization classification of tumours of haematopoietic and lymphoid tissues. World Health Organization, Lyon, S 127–129Google Scholar
  125. 125.
    Walter RB, Othus M, Burnett AK et al (2013) Significance of FAB subclassification of „acute myeloid leukemia, NOS“ in the 2008 WHO classification: analysis of 5848 newly diagnosed patients. Blood 121:2424–2431PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Walter RB, Othus M, Paietta EM et al (2015) Effect of genetic profiling on prediction of therapeutic resistance and survival in adult acute myeloid leukemia. Leukemia 29:2104–2107PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Welch JS, Ley TJ, Link DC et al (2012) The origin and evolution of mutations in acute myeloid leukemia. Cell 150:264–278PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Wong TN, Ramsingh G, Young AL et al (2015) Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature 518:552–555PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Xu Y, McKenna RW, Wilson KS, Karandikar NJ, Schultz RA, Kroft SH (2006) Immunophenotypic identification of acute myeloid leukemia with monocytic differentiation. Leukemia 20:1321–1324PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Yeasmin S, Nakayama K, Ishibashi M, Oride A, Katagiri A, Purwana IN, Iida K, Nakayama N, Ishikura H, Miyazaki K (2008) Therapy-related myelodysplasia and acute myeloid leukemia following paclitaxel- and carboplatin-based chemotherapy in an ovarian cancer patient: a case report and literature review. Int J Gynecol Cancer 18:1371–1376PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Zhang MY, Churpek JE, Keel SB et al (2015) Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nat Genet 47:180–185PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Institut für PathologieMedizinische Hochschule Hannover (MHH)HannoverDeutschland

Personalised recommendations