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Acute Myeloid Leukemia with the t(8;21) Translocation: Clinical Consequences and Biological Implications

By Håkon Reikvam, Kimberley Joanne Hatfield, Astrid Olsnes Kittang, Randi Hovland and Øystein Bruserud

Abstract

The t(8;21) abnormality occurs in a minority of acute myeloid leukemia (AML) patients. The translocation results in an in-frame fusion of two genes, resulting in a fusion protein of one N-terminal domain from the AML1 gene and four C-terminal domains from the ETO gene. This protein has multiple effects on the regulation of the proliferation, the differentiation, and the viability of leukemic cells. The translocation can be detected as the only genetic abnormality or as part of more complex abnormalities. If t(8;21) is detected in a patient with bone marrow pathology, the diagnosis AML can be made based on this abnormality alone. t(8;21) is usually associated with a good prognosis. Whether the detection of the fusion gene can be used for evaluation of minimal residual disease and risk of leukemia relapse remains to be clarified. To conclude, detection of t(8;21) is essential for optimal handling of these patients as it has both diagnostic, prognostic, and therapeutic implications

Topics: Review Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3100545
Provided by: PubMed Central

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Citations

  1. (2005). a c h e r ,W .K e r n ,S .S c h n i t t g e r ,W .H i d d e m a n n ,T .H a f e r
  2. (2008). A correlation study of immunophenotypic, cytogenetic, and clinical features
  3. (2007). A distinct epigenetic signature at targets of a leukemia protein,” BMC Genomics,v o l .8 ,a r t i c l e 38,
  4. (2010). A novel exon in AML1-ETO negatively influences the clonogenic potential of the t(8;21) in acute myeloid leukemia,”
  5. (2006). A previously unidentified alternatively spliced isoform of t(8;21) transcript promotes leukemogenesis,”
  6. (2002). A white blood cell index as the main prognostic factor in t(8;21) acute myeloid leukemia (AML):a survey of 161cases from the French AML intergroup,”
  7. (1994). Activation of the leukocyte plastin gene occurs in most human cancer cells,”
  8. (2003). Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair,”
  9. Acute myeloid leukemia harboring t(8;21)(q22;q22): a heterogeneous disease with poor outcome in a subset of patients unrelated to secondary cytogeneticaberrations,”ModernPathology,vol.21,no.8,pp.1029– 1036, 2008.22
  10. (2009). Acute myeloid leukemia with translocation (8;21) or inversion (16) in elderly patients treated with conventional chemotherapy: a collaborative study of the French CBF-AML intergroup,”
  11. (2008). Advances in molecular genetics and treatment of corebinding factor acute myeloid leukemia,”
  12. (2006). Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B study,”
  13. (2009). Aleukaemic acute myeloid leukaemia with t(8;21)(q22;q22): images in haematology,”
  14. (2007). Aleukemia fusion protein attenuates thespindlecheckpointandpromotesaneuploidy,”
  15. (2002). All-trans retinoic acid as a single agent induces complete remission in a patient withacute leukemiaofM subtype,”
  16. (2008). Allogeneic hematopoietic stem-cell transplantation for myeloid sarcoma: a retrospective study from the SFGM-TC,”
  17. (2009). Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation,”
  18. Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR24/MKP-7/MAPK network,”
  19. (2004). AML1-ETO decreases ETO-2 (MTG16) interactions with nuclear receptor corepressor, an effect that impairs granulocyte differentiation,”
  20. (2005). AML1-ETO fusion protein up-regulates TRKA mRNA expression in human CD34+ cells, allowing nerve growth factor-induced
  21. (2000). AML1-MTG8 leukemic protein induces the expression of granulocyte colony-stimulating factor (G-CSF) receptor through the upregulation of CCAAT/enhancer binding protein epsilon,”
  22. (1999). An unusual case of intrapulmonary granulocytic sarcoma presenting as interstitial pneumonitis following allogeneic bone marrow transplantation for acute myeloid leukaemia and responding to donor lymphocyte infusion,”
  23. (2008). and D.E.Zhang,“T(8;21)(q22;q22)fusionproteinspreferentially bind to duplicated AML1/RUNX1 DNA-binding sequences to differentially regulate geneexpression,”
  24. (2008). and FLT3 receptor tyrosine kinase mutations in acute myeloid leukemia with favorable cytogenetics: two novel mutations and selective occurrence in leukemia subtypes and age groups,” Experimental and Molecular Pathology,
  25. (2006). and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood
  26. (2007). Association between prenatal pesticide exposures and the generation of leukemia-associated
  27. (2000). Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration,”
  28. (2010). Avariant allele of growth factor independence 1 (GFI1) is associated with acute myeloid leukemia,”
  29. (2006). Avent´ ın et al., “Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics
  30. (2002). B.T.Gjertsen,A.M.Øyan,B.Marzolfetal.,“Analysisofacute myelogenous leukemia: preparation of samples for genomic and proteomic analyses,”
  31. (2010). Bone marrow cellularityisa singlemostimportantindependent prognostic factor
  32. (2011). Braekeleer, “RUNX1 translocations and fusion genes in malignant hemopathies,”
  33. (2002). Buffler et al., “In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia,”
  34. (2003). C a r e ,P .J .M .V a l k ,A .C .G o o d e v ee ta l . ,“ I n c i d e n c e and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias,”
  35. (2005). c h e s s l ,V .P .S .R a w a t ,M .C u s a ne ta l .
  36. (2007). c h n i t t g e r ,U .B a c h e r ,W .K e r n ,T .H a f e r l a c h ,a n dC .
  37. (2009). Cathepsin W expressed exclusively in CD8+ T cells and NK cells, is secreted during target cell killing but is not essential for cytotoxicity in human CTLs,”
  38. (2004). Caveolin-1 gene is coordinately regulated with the multidrug resistance 1 gene in normal and leukemic bone marrow,”
  39. (2009). CBFβ is critical for AML1-ETO and
  40. (2008). CEBPA polymorphisms and mutations in patients with acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and non-Hodgkin’s lymphoma,”
  41. (2004). Cemeriki´ ce ta l . ,“ G r a n u l o c y t i c sarcoma of the brain in a patient with acute myeloid leukemia,”Actachirurgica Iugoslavica.,vol.51,no.3,pp.129– 131,
  42. Characterisation of AML1-ETO9A leukaemiogenesis using an inducible murinemodel,” Haematologica, vol.95,no. s2,2010,abstract no 0025.
  43. (2002). Characteristics and outcome of t(8;21)-positive childhood acute myeloid leukemia: a single institution’s experience,”
  44. (2008). Clinical characteristics and outcomes in patients with t(8;21) acute myeloid leukemia in
  45. (2008). Clinical significance of minimal residual disease in patients with t(8;21) acute myeloid leukemia in
  46. (2008). Clinical significance of themostcommonchromosometranslocationsinadultacute myeloid leukemia,”
  47. (2010). Combination of intensive chemotherapy and anticancer vaccines in the treatment of human malignancies: the hematological experience,”
  48. Comparison between conventional banding analysis and FISH screening with an AML-specific set of probes in 260 patients,”
  49. (2001). Comparison of outcome in acute myelogenous leukemia patients with translocation (8;21) found by standard cytogenetic analysis and patients with AML1/ETO fusion transcript found only by PCR testing,”
  50. (2009). Connexins are active participants of hematopoietic stem cell regulation,”
  51. (2008). Cooperating mutations of receptor tyrosine kinases and Ras genes in childhood core-binding factor acute myeloid leukemia and a comparative analysis on paired diagnosis and relapse samples,”
  52. (2009). Cytogenetic profile of de novo acute myeloidleukemia:a study based on 1432 patients in asingleinstitutionofChina,”Leukemia,vol.23,no.10,pp. 1801–1806,
  53. (2000). Cytogenetically cryptic AML1—ETO and CBFβ—MYH11 gene rearrangements: incidence in 412 cases of acute myeloid leukaemia,”
  54. (2010). Cytogenetics of childhood acute myeloid leukemia:
  55. (2010). D¨ ohner et al., “Quantitative DNA methylation predicts survival in adult acute myeloid leukemia,”
  56. (2005). D.A.Sweetser,A.J.Peniket,C.Haalandetal.,“Delineationof theminimalcommonlydeleted segmentandidentificationof candidate tumor-suppressor genes in del(9q) acute myeloid leukemia,”GenesChromosomesand Cancer,
  57. (2005). De Locht et al., “Transcriptional repression of the neurofibromatosis-1 tumor suppressor by the t(8;21) fusion protein,”
  58. (2006). Decreased intranuclear mobility of acute myeloid leukemia 1-containing fusion proteins is accompanied by reduced mobility and compartmentalization of core binding factor β,”
  59. (2009). Definitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting and transactivation,”
  60. (2005). Del(9q) AML: clinical and cytological characteristics and prognostic implications,”
  61. (2010). Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel,
  62. (2006). Diagnosis and monitoring of AML1-MTG8 (ETO)-positive acute myeloid leukemia by qualitative and real-time quantitative
  63. (2002). Diagnostic detection of AML1/ETO gene fusion by polymerase chain reaction,”
  64. (2010). Differential contributions of c-kit activating mutations to promotion of AML1-ETO associated neoplasia,”
  65. (2010). Differential cytogenomics and miRNA signature of the Acute Myeloid Leukaemia
  66. (2006). Disease-specific expression of VEGF and its receptors in AML cells: possible autocrine pathway of VEGF/type1 receptor
  67. (2008). Disruption of the NHR4 domain structure in AML1-ETO abrogates SON binding and promotes leukemogenesis,”
  68. (2008). Distinct microRNA expression profiles in acute myeloid leukemia with common translocations,”
  69. (2010). DNA methylation profilesandtheirrelationshipwithcytogenetic statusinadult acute myeloid leukemia,”
  70. (2010). DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia,”
  71. (2011). E.Ersvaer,K.Hatfield,H.Reikvam,andO.Bruserud,“Future perspectives: therapeutic targeting of NOTCH signalling may become a strategy in patients receiving stem cell transplantationforhematologicmalignancies,”BoneMarrow Research,
  72. (2000). Ernst,“New strategies inthe treatment ofacute myelogenous leukemia: mobilization and transplantation of autologous peripheral blood stem cells in adult patients,”
  73. (2009). Erpelinck et al., “Prediction of molecular subtypes in acute myeloidleukemia based on gene expression profiling,”
  74. (2004). ETO interacting proteins,”
  75. (2000). Evaluation of minimal residual disease using reverse-transcription polymerasechain reaction int(8;21)acutemyeloidleukemia: a multicenter study of 51 patients,”
  76. (2006). Expression of B cell-specific activator protein/PAX5 in acute myeloid leukemia with t(8;21)(q22;q22),”
  77. (2010). F o r t i e r ,J .E .P a y t o n ,P .C a h a n
  78. (2009). Flow cytometric immunobead assay for the detection of BCR-ABL fusion proteins
  79. (2005). G o e m a n s ,C H .M .Z w a a n ,M .M i l l e re ta l . ,“ M u t a t i o n s in KIT andRAS are frequent events in pediatric core-binding factor acute myeloid leukemia,”
  80. Gelsolin superfamily proteins: key regulators of cellular functions,”
  81. (2007). Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia,”
  82. (2010). Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model,”
  83. (2000). Good outcome of children with acute myeloid leukemia and t(8;21)(q22;q22), even when associated with granulocytic sarcoma: a report from a single institution in
  84. (2005). Gradel-Duflos et al., “Prognostic value of real-time quantitative PCR (RQ-PCR)
  85. (2008). Granulocytic sarcoma causing cord compression in a pregnant woman with acute myeloid leukemia and t(8;21),”
  86. (2004). Granulocytic sarcoma presenting as pneumonia in a child with t(8;21) acute myelogenous leukemia: diagnosis by flourescent in situ hybridization,”
  87. (1981). Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases,”
  88. (2009). Growth inhibition of AML cells with specific chromosome abnormalities by monoclonal antibodies to receptors for vascular endothelial growth factor,”
  89. (2011). h o u ,M .W u n d e r l i c h ,A .G r i e s i n g e r ,a n dJ .C .M u l l o y , “N-RasG12D induces features of stepwise transformation in preleukemic humanumbilicalcordbloodcultures expressing theAML1-ETOfusiongene,” Blood,vol.117,no.7,pp.2237– 2240,
  90. (2006). Haferlach et al., “KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival,”
  91. (2008). Health Organization Classification of Tumors of Haematopoietic and Lymphoid Tissues, International Agency for Cancer,
  92. (2005). Heart and muscle involvement by extra-medullary myeloid leukemia: a case report and review of the literature,”
  93. (2007). Histone deacetylase inhibitors in cancer treatment: a review of the clinical toxicity and the modulation of gene expression in cancer cells,”
  94. (2005). i a o ,S .L i u ,X .L i u ,M .Y u ,a n dY .H a o ,“ T e t r a p l o i d y or near-tetraploidy clones with double 8;21 translocation: a non-random additional anomaly of acute myeloid leukemia with t(8;21)(q22;q22),” Haematologica,v o l .9 0 ,n o .3 ,p p .
  95. (2007). i c h m a n n ,L .C h e n ,M .H e i n r i c he ta l . ,“ T a r g e t i n gt h e oligomerizationdomainofETOinterferes withRUNX1/ETO oncogenic activity in t(8;21)-positive leukemic cells,”
  96. (2005). i d d i a r d ,R .H i l l s ,A .K .B u r n e t t ,R .L .D a r l e y ,a n d A. Tonks, “OGG1 is a novel prognostic indicator in acute myeloid leukaemia,”
  97. (2001). i e i r a ,V .O l i v e i r a ,A .P .A m b r ´ osio et al., “Translocation (8;17;15;21)(q22;q23;q15;q22) in acute myeloid leukemia (M2): a four-way variant of t(8;21),” Cancer Genetics and Cytogenetics,vol.
  98. (2008). Identification and characterization of novel AML1-ETO fusion transcripts in pediatric t(8;21) acute myeloid leukemia: a report from the Children’s Oncology
  99. (1973). Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia,”
  100. (2007). Immunophenotypic profile predictive off KIT activating mutations in AML1-ETO leukemia,”
  101. (2008). In vivo biological effects of
  102. (2006). Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia
  103. (2004). Insertions generating the 5 RUNX1/3 C8FA2T1 gene in acute myeloid leukemia cases show variable breakpoints,”
  104. (2010). Integrative meta-analysisofdifferentialgeneexpressionin acutemyeloid leukemia,”
  105. (2010). KIT mutations confer a distinct gene expression signature in core binding factor leukaemia: research paper,”
  106. (1994). Kn¨ obl et al., “AML1/ETO fusion mRNA can be detected in remission blood samples of all patients with t(8;21) acute myeloid leukemia after chemotherapy or autologous bone marrow transplantation,”
  107. (1996). l a m p f e r ,J .Z h a n g ,A .O .Z e l e n e t z ,H .U c h i d a ,a n d
  108. (2004). l a u s ,T .H a f e r l a c h ,S .S c h n i t t g e r ,W .K e r n ,W .H i d -demann, and
  109. (2010). L e y ,L .D i n g ,M .J .W a l t e re ta l .
  110. (1998). l s t e d ,a n dS .W .H i e b e r t ,“
  111. (2004). L.Bullinger,K.D¨ ohner,E.Bairetal.,“Useofgene-expression profiling to identify prognostic subclasses in adult acute myeloidleukemia,”TheNewEngland
  112. (2004). Laudes et al., “ETO/MTG8 is an inhibitor of C/EBPβ activity and a regulator of early adipogenesis,”
  113. (2007). Leukemia associated antigens: their dual role as biomarkers and immunotherapeutic targets for acute myeloid leukemia,”
  114. (2006). Leukemogenic AML1-ETO fusion protein upregulates expression of connexin 43: t h er o l ei nA M L1 - E T O - i n d u c e dg r o w t ha r r e s ti nl e u k e m i c cells,”
  115. (1994). Liu Yin, “Detection of t(8;21) by reverse transcriptase polymerase chain reaction in patients in remission of acute myeloid leukaemia type M2 after chemotherapy or bone marrow transplantation,”
  116. (2005). Long-term results of children with acute myeloid leukemia: a report of three consecutive Phase III trials by the Children’s Cancer Group:
  117. (2006). Low p53 expression of acute myelocytic leukemia cells with
  118. (2008). M.Kantarjian,S.Wenet al.,“Myeloid sarcoma is associated with superior event-free survival and o v e r a l ls u r v i v a lc o m p a r e dw i t ha c u t em y e l o i dl e u k e m i a ,
  119. Mart´ ınez-Ram´ ı r e z ,J .C .C i g u d o s ae ta l . , “Identification of ins(8;21) with AML1/ETO fusion in acute myelogenous leukemia M2 by molecular cytogenetics,”
  120. (2008). MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia,”
  121. (2006). Mizushimaetal.,“Commongene expression signatures in t(8;21)- and inv(16)-acute myeloid leukaemia,”
  122. (2009). Molecular detection of AML1-MTG8-positive cells in peripheral blood from a patient with isolated extramedullary relapse of t(8;21) acute myeloid leukemia,”
  123. (2008). Molecular origins of cancer: epigenetics in cancer,” The New England
  124. (1998). Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia,”
  125. (2009). Mutations in the Fms-related tyrosine kinase 3 (FLT3) gene independently predict pooroutcomeinacutemyeloidleukemia(AML)with t(8;21): a study of the outcome in acute myeloid leukemia (AML) with t(8;21): a study of the German-Austrian
  126. (2007). Myeloid sarcoma: clinico-pathologic,phenotypicandcytogenetic analysisof92 adult patients,”
  127. (2005). Myelomastocytic leukemia: evidence for the origin of mast cells from the leukemic clone and eradication by allogeneic stem cell transplantation,”
  128. (2007). Neoplastic mast cells in systemic mastocytosis associated with t(8;21) acute myeloid leukemia are derived from the leukemic clone,”
  129. (2010). Neuhoff,D .R e i n h a r d t ,A .S a n d e re ta l . ,“ P r o g n o s t i c impact of specific chromosomalaberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial
  130. (2010). New prognostic markers in acute myeloid leukemia: perspective from the clinic,” Hematology American SocietyofHematologyEducationProgram,vol.2010,no.1,pp.
  131. (2003). New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFB-MYH11 acute myeloid leukemia based on quantification of fusion transcripts,”
  132. Novel role of HDAC inhibitors in AML1/ETO AML cells: activation of apoptosis and phagocytosis through induction of annexin A1,” Cell DeathandDifferentiation,vol.14,no.8,pp.1443–1456,2007.
  133. (2009). Nuclear factor-B signaling: a contributor in leukemogenesis and a target for pharmacological interventioninhumanacutemyelogenousleukemia,”CriticalReviews in Oncogenesis,
  134. (2005). o z u ,T .F u k u y a m a ,T .Y a m a m i ,K .A k a g i ,a n dY .K a n e k o , “MYND-less splice variants of AML1-MTG8 (RUNX1-CBFA2T1) are expressed
  135. (2006). ohner, “JAK2V617F mutations as cooperative genetic lesions in t(8;21)-positive acute myeloid leukemia,”
  136. (2007). Oliveira,M.B.Vianaet al.,“Prognostic significance of WT1 gene expression in pediatric acute myeloid leukemia,”
  137. (2004). Orleth et al., “PAX5 expression in acute leukemias: higher B-lineage specificity than CD79a and selective association with t(8;21)-acute myelogenous leukemia,”
  138. (2007). Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention,”
  139. (2007). P e t e r s o n ,A .B o y a p a t i ,E .Y .A h ne ta l . ,“ A c u t em y e l o i d leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts,”
  140. (2006). P l e v i n ,J .Z h a n g ,C .G u o ,R .G .R o e d e r ,a n dM .I k u r a , “The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBPassociated factor homology domain,”
  141. (2008). P´ erez et al., “HLAidentical sibling allogeneic transplants versus chemotherapy in acute myelogenous leukemia with t(8;21) in first complete remission: collaborative study between the German
  142. (2008). P53 signaling in response to increased DNA damage sensitizes AML1-ETO cellstostress-induced death,”Blood,vol.111,no.4,pp.2190– 2199,
  143. (1996). Persistence of multipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21) acute myelogenous leukemia,”
  144. (1993). Persistence of the 8;21 translocation in patients with acute myeloid leukemiatype
  145. (1996). Persistence of the AML1/ETO fusion transcript in patients treated with allogeneic bone marrow transplantation for t(8;21) leukemia,”
  146. (2010). Persistent altered fusion transcript splicing identifies RUNX1-RUNX1T1+ AML patients likely to relapse,”
  147. (2010). Pharmacological targeting of the PI3KAKT/PKB-mTOR pathway alters local angioregulation in acute myelogenous leukemia,”
  148. (2005). PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects,”
  149. (2009). Preferred colocalization of chromosome 8 and 21 in myeloid bone marrow cells detected by three dimensional molecular cytogenetics,”InternationalJournal
  150. (1997). Presence of t(8;21)(q22;q22) in myeloperoxidasepositive, myeloid surface antigen-negative acute myeloid leukemia,”
  151. (2010). Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial
  152. (2010). Profilingof histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia,”
  153. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study,”
  154. (2009). Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenictrioxidetherapy,”
  155. (2006). Proteomics of acute myeloid leukaemia: cytogenetic risk groups differ specifically in their proteome, interactome and posttranslational protein modifications,”
  156. (1999). R a i m o n d i ,M .N .C h a n g ,Y .R a v i n d r a n a t he ta l . , “Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a Cooperative Pediatric Oncology Group studyPOG 8821,” Blood,
  157. (1992). r i c k s o n ,J .G a o ,K .S .C h a n ge ta l . ,“ I d e n t i fi c a t i o no f breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentationgene,
  158. (2003). r u s e r u d ,R .H o v l a n d ,L .W e r g e l a n d ,T .S .H u a n g ,a n d
  159. (2005). Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bonemarrowtransplantationinfirstcompleteremission:the
  160. (2008). Review: genetic models of acute myeloid leukaemia,”
  161. S a n d e r s o n ,P .R .E .J o h n s o n ,A .V .M o o r m a ne ta l . , “Population-based demographic study of karyotypes in 1709 patients with adult acute myeloid leukemia,” Leukemia,v o l .
  162. (2009). s m a n ,V .G o b e r t ,F .P o n t h a n ,O .H e i d e n r e i c h
  163. (2006). S.Schnittger,T.Looketal.,“Identificationof additional cytogenetic and molecular genetic abnormalities inacute myeloidleukaemiawitht(8;21)/AML1-ETO,”British
  164. (2010). Sohn et al., “Re-analysis of the outcomes of post-remission therapy for acute myeloid leukemia with core binding factor according to years of patient enrollment,” Japanese journal of clinical oncology,v o l .
  165. (1999). Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia,”
  166. Strikingly different molecular relapse kinetics
  167. (2009). Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity,”
  168. (2009). Suzukiet al.,“Hematopoietic stem cell transplantation for core binding factor acute myeloid leukemia: T(8;21) and inv(16) represent different clinical outcomes,”
  169. (1996). Synergistic up-regulation of the myeloid-specific promoterJournal of Biomedicine and Biotechnology 19 for the macrophage colony-stimulating factor receptor by AML1 and the t(8;21) fusion protein may contribute to leukemogenesis,”
  170. Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia,”
  171. (2008). Systemic mastocytosis with plasma cell dyscrasia: report of a case,”
  172. (2010). T.Corpora,L.Roudaia,M.Ooetal.,“Structure oftheAML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity,”
  173. (2006). t(8;21) acute myeloid leukaemiacellsaredependent onvascularendothelialgrowth factor (VEGF)/VEGF receptor type2 pathway and phosphorylation of Akt,”
  174. (2007). Targeting AML1/ETO-histone deacetylase repressor complex: a novel mechanism for valproic acid-mediated gene expression and cellular differentiation in AML1/ETO-positive acute myeloid leukemia cells,”
  175. (2007). Targeting receptor tyrosine kinasesignalingin acute myeloid leukemia,”
  176. (2006). The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations,”
  177. (2005). The co-expression of PML/RARα and AML1/ETO fusion genes is associated with ATRA resistance,”
  178. (2009). The gene encoding thioredoxininteracting protein (TXNIP) is a frequent virus integration siteinvirus-induced mouseleukemiaandis overexpressed in a subset of AML patients,”Leukemia
  179. (2008). The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes,” J o u r n a lo fC e l lS c i e n c e ,
  180. (2003). The myeloid master regulator transcription factor PU.1 is inactivated by
  181. (2004). The oncogenic fusion protein RUNX1-CBFA2T1 supports proliferation and inhibits senescence in t(8;21)-positive leukaemic cells,”
  182. (2007). The p21 pathway is involved in blocking leukemogenesis by the t(8;21) fusion protein
  183. (2009). The role of multiparameter flow cytometry for detection of minimal residual disease in acute myeloid leukemia,”
  184. (2008). The semaphorins: versatile regulators of tumour progression and tumour angiogenesis,”
  185. (2005). The t(8;21) translocation converts AML1 into a constitutive transcriptional repressor,”
  186. (2009). Therapy-related acute myeloid leukemia after concurrent chemoradiotherapy for esophageal cancer: report of two cases,”
  187. (2009). Therapyrelated acute myeloid leukemia with t(8;21) (q22;q22) shares many features with de novo acute myeloid leukemia with t(8;21)(q22;q22) but does not have a favorable outcome,”
  188. (2009). Total serum tryptase: a predictive marker for KIT mutation in acute myeloid leukemia,” Leukemia Research,v o l .3 3 ,n o .9 ,p p .
  189. (2005). Treatment and longtermresults inchildren withacute myeloidleukaemiatreated according to
  190. (2005). Treatment of childhood acute myeloblastic leukemia: dose intensification improves outcome and maintenance therapy is of no benefit—multicenter studies of the French LAME(Leuc´ emieAigu¨ eM y´ eloblastiqueEnfant)Cooperative
  191. (2007). Two cases of secondary acute myeloid leukemia accompanying adult T-cell leukemia/lymphoma,”
  192. (2007). u ,D .L i ,Y .L u ,a n dG .Q .C h e n ,“ L e u k e m o g e n i cA
  193. (2007). Utility ofinterphase FISH to stratify patients into cytogenetic risk categories at diagnosis of AML
  194. (2004). V a l k ,R .G .W .V e r h a a k ,M .A .B e i j e ne ta l . ,“ P r o g -nostically useful gene-expression profiles in acute myeloid leukemia,”TheNew
  195. (2003). van der Velden et al.,“Standardization and quality control studies of ’real time’ quantitative reverse transcriptase polymerase chain reaction of fusion genetranscripts forresidualdiseasedetection inleukemia—a
  196. (2007). Verdonck et al., “Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom?”
  197. (2005). W a n g ,G .B .Z h o u ,T .Y i ne ta l .
  198. (2001). Y.Yuan,L.Zhou,T.Miyamoto et al.,“AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations,”
  199. (2007). Zardo et al., “Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETOoncoprotein,”CancerCell,vol.12,no.5,pp.457– 466,