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Cited by 49Acute Myeloid Leukemia ResearchRetinoids in leukemia and cellular processesChronic Myeloid Leukemia Treatments

Erythroleukemia-historical perspectives and recent advances in diagnosis and management

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Boddu, Prajwal, Benton, Christopher B., Wang, Wei, Borthakur, Gautam, Khoury, Joseph D., Pemmaraju, Naveen·2018·Blood Reviews
DOI 10.1016/j.blre.2017.09.002PMC PMC5857409
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Abstract

Acute erythroleukemia is a rare form of acute myeloid leukemia recognized by its distinct phenotypic attribute of erythroblastic proliferation. After a century of its descriptive history, many diagnostic, prognostic, and therapeutic implications relating to this unique leukemia subset remain uncertain. The rarity of the disease and the simultaneous involvement of its associated myeloid compartment have complicated in vitro studies of human erythroleukemia cell lines. Although murine and cell line erythroleukemia models have provided valuable insights into pathophysiology, translation of these concepts into treatment are not forthcoming. Integration of knowledge gained through a careful study of these models with more recent data emerging from molecular characterization will help elucidate key mechanistic pathways and provide a much needed framework that accounts for erythroid lineage-specific attributes. In this article, we discuss the evolving diagnostic concept of erythroleukemia, translational aspects of its pathophysiology, and promising therapeutic targets through an appraisal of the current literature.

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  • Three distinct clusters of HSPCs were identified in TP53-sAML, including one characterized by overexpression of erythroid genes.

    “Three distinct clusters of HSPCs were identified in TP53-sAML, including one characterized by overexpression of erythroid genes, of particular note as erythroleukemia is a rare entity, associated with adverse outcomes and TP53 mutation43,44.”

    From Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution (2023) · cites this paper as [43]

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  1. [1]Schwartz SO Critchlow J Erythremic myelosis (DI Guglielmo’s disease); critical review with report of four cases, and comments on erythroleukemia Blood 1952 7 8 765 93 14934762
  2. [2]Dameshek W Baldini M The Di Guglielmo syndrome Blood 1958 13 192 4 13510296
  3. [3]Bain BJ Di Guglielmo and his syndromes Br J Haematol 2003 120 939 43 12648062
  4. [4]Dameshek W Some speculations on the myeloproliferative syndromes Blood 1951 6 4 372 5 14820991
  5. [5]Dameshek W The DiGuglielmo syndrome revisited Blood 1969 34 5 567 72 5260599
  6. [6]Heath CW Jr Bennett JM Whang-Peng J Berry EW Wiernick PH Cytogenetic findings in erythroleukemia Blood 1969 33 3 453 67 5250293
  7. [7]Dyment PG Melnyk J Brubaker CA A cytogenetic study of acute erythroleukemia in children Blood 1968 32 6 997 1002 5248296
  8. [9]Vardiman JW Thiele J Arber DA Brunning RD Borowitz MJ Porwit A The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes Blood 2009 114 5 937 51 19357394
  9. [10]Bennett JM Catovsky D Daniel MT Flandrin G Galton DA Gralnick HR Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group Br J Haematol 1976 33 4 451 8 188440
  10. [11]Villeval JL Cramer P Lemoine F Henri A Bettaieb A Bernaudin F Phenotype of early erythroblastic leukemias Blood 1986 68 5 1167 74 2945604
  11. [12]Hasserjian RP Howard J Wood A Henry K Bain B Acute erythremic myelosis (true erythroleukaemia): a variant of AML FAB-M6 J Clin Pathol 2001 54 3 205 9 11253132 PMC1731380
  12. [14]Harris NL Jaffe ES Diebold J Flandrin G Muller-Hermelink HK Vardiman J World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997 J Clin Oncol 1999 17 12 3835 49 10577857
  13. [15]Park S Picard F Azgui Z Viguie F Merlat A Guesnu M Erythroleukemia: a comparison between the previous FAB approach and the WHO classification Leuk Res 2002 26 5 423 9 11916513
  14. [16]van Krieken JH The 2008 WHO-classification: small and big changes! J Hematop 2009 2 2 63 19684870 PMC2725289
  15. [17]Bacher U Haferlach C Alpermann T Kern W Schnittger S Haferlach T Comparison of genetic and clinical aspects in patients with acute myeloid leukemia and myelodysplastic syndromes all with more than 50% of bone marrow erythropoietic cells Haematologica 2011 96 9 1284 92 21606170 PMC3166098
  16. [18]Arber DA Revisiting erythroleukemia Curr Opin Hematol 2016 24 2 2017 3 146 151 27875373
  17. [19]Mazzella FM Kowal-Vern A Shrit MA Wibowo AL Rector JT Cotelingam JD Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis Am J Clin Pathol 1998 110 5 590 8 9802343
  18. [20]Liu W Hasserjian RP Hu Y Zhang L Miranda RN Medeiros LJ Pure erythroid leukemia: a reassessment of the entity using the 2008 World Health Organization classification Mod Pathol 2011 24 3 375 83 21102413
  19. [21]Kowal-Vern A Cotelingam J Schumacher HR The prognostic significance of proerythroblasts in acute erythroleukemia Am J Clin Pathol 1992 98 1 34 40 1615923
  20. [22]Wang W Wang SA Medeiros LJ Khoury JD Pure Erythroid Leukemia Am J Hematol 2017 3 92 3 292 296 28006859
  21. [23]Wang W Grier DD Woo J Ward M Sui G Torti SV Ferritin H is a novel marker of early erythroid precursors and macrophages Histopathology 2013 62 6 931 40 23611361
  22. [24]Dong HY Wilkes S Yang H CD71 is selectively and ubiquitously expressed at high levels in erythroid precursors of all maturation stages: a comparative immunochemical study with glycophorin A and hemoglobin A Am J Surg Pathol 2011 35 5 723 32 21415701
  23. [25]Santos FP Faderl S Garcia-Manero G Koller C Beran M O’Brien S Adult acute erythroleukemia: an analysis of 91 patients treated at a single institution Leukemia 2009 23 12 2275 80 19741728 PMC4217206
  24. [26]Welch JS Petti AA Miller CA Fronick CC O’Laughlin M Fulton RS TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes N Engl J Med 2016 375 21 2023 36 27959731 PMC5217532
  25. [28]Ko PS Liu YC Yeh CM Gau JP Yu YB Hsiao LT The uniqueness of morphological features of pure erythroid leukemia in myeloid neoplasm with erythroid predominance: A reassessment using criteria revised in the 2016 World Health Organization classification PLoS One 2017 12 2 e0172029 28196090 PMC5308818
  26. [29]Montalban-Bravo G Benton CB Wang SA Ravandi F Kadia T Cortes J Greater than one TP53 abnormality is a dominant characteristic of pure erythroid leukemia Blood 2017 5 4 129 18 2584 2587 28246192 PMC5418636
  27. [30]Hasserjian RP Zuo Z Garcia C Tang G Kasyan A Luthra R Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification Blood 2010 115 10 1985 92 20040759 PMC2942006
  28. [31]Grove CS Vassiliou GS Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer? Dis Model Mech 2014 7 8 941 51 25056697 PMC4107323
  29. [32]Ney PA D’Andrea AD Friend erythroleukemia revisited Blood 2000 96 12 3675 80 11090047
  30. [33]Ben-David Y Bernstein A Friend virus-induced erythroleukemia and the multistage nature of cancer Cell 1991 66 5 831 4 1889087
  31. [34]Ruscetti SK Deregulation of erythropoiesis by the Friend spleen focus-forming virus Int J Biochem Cell Biol 1999 31 10 1089 109 10582341
  32. [35]Li JP D’Andrea AD Lodish HF Baltimore D Activation of cell growth by binding of Friend spleen focus-forming virus gp55 glycoprotein to the erythropoietin receptor Nature 1990 343 6260 762 4 2154701
  33. [36]Nishigaki K Thompson D Hanson C Yugawa T Ruscetti S The envelope glycoprotein of friend spleen focus-forming virus covalently interacts with and constitutively activates a truncated form of the receptor tyrosine kinase Stk J Virol 2001 75 17 7893 903 11483734 PMC115033
  34. [37]Prasher JM Elenitoba-Johnson KS Kelley LL Loss of p53 tumor suppressor function is required for in vivo progression of Friend erythroleukemia Oncogene 2001 20 23 2946 55 11420707
  35. [38]Moreau-Gachelin F Wendling F Molina T Denis N Titeux M Grimber G Spi-1/PU.1 transgenic mice develop multistep erythroleukemias Mol Cell Biol 1996 16 5 2453 63 8628313 PMC231234
  36. [40]Starck J Doubeikovski A Sarrazin S Gonnet C Rao G Skoultchi A Spi-1/PU.1 is a positive regulator of the Fli-1 gene involved in inhibition of erythroid differentiation in friend erythroleukemic cell lines Mol Cell Biol 1999 19 1 121 35 9858537 PMC83871
  37. [41]Villeval JL Mitjavila MT Dusanter-Fourt I Wendling F Mayeux P Vainchenker W Autocrine stimulation by erythropoietin (Epo) requires Epo secretion Blood 1994 84 8 2649 62 7919379
  38. [42]Mitjavila MT Le Couedic JP Casadevall N Navarro S Villeval JL Dubart A Autocrine stimulation by erythropoietin and autonomous growth of human erythroid leukemic cells in vitro J Clin Invest 1991 88 3 789 97 1653276 PMC295463
  39. [43]Drexler HG Matsuo Y MacLeod RA Malignant hematopoietic cell lines: in vitro models for the study of erythroleukemia Leuk Res 2004 28 12 1243 51 15475063
  40. [44]Papayannopoulou T Nakamoto B Kurachi S Tweeddale M Messner H Surface antigenic profile and globin phenotype of two new human erythroleukemia lines: characterization and interpretations Blood 1988 72 3 1029 38 3166384
  41. [45]Grossman Z The stem cell concept revisited: self-renewal capacity is a dynamic property of hemopoietic cells Leuk Res 1986 10 8 937 50 3528681
  42. [46]Laslo P Spooner CJ Warmflash A Lancki DW Lee HJ Sciammas R Multilineage transcriptional priming and determination of alternate hematopoietic cell fates Cell 2006 126 4 755 66 16923394
  43. [48]Yamada T Kihara-Negishi F Yamamoto H Yamamoto M Hashimoto Y Oikawa T Reduction of DNA binding activity of the GATA-1 transcription factor in the apoptotic process induced by overexpression of PU.1 in murine erythroleukemia cells Exp Cell Res 1998 245 1 186 94 9828115
  44. [49]Cantor AB Orkin SH Transcriptional regulation of erythropoiesis: an affair involving multiple partners Oncogene 2002 21 21 3368 76 12032775
  45. [50]Yamada T Kondoh N Matsumoto M Yoshida M Maekawa A Oikawa T Overexpression of PU.1 induces growth and differentiation inhibition and apoptotic cell death in murine erythroleukemia cells Blood 1997 89 4 1383 93 9028962
  46. [51]Kihara-Negishi F Yamada T Kubota Y Kondoh N Yamamoto H Abe M Down-regulation of c-myc and bcl-2 gene expression in PU.1-induced apoptosis in murine erythroleukemia cells Int J Cancer 1998 76 4 523 30 9590129
  47. [53]Rosenbauer F Wagner K Kutok JL Iwasaki H Le Beau MM Okuno Y Acute myeloid leukemia induced by graded reduction of a lineage-specific transcription factor, PU.1 Nat Genet 2004 36 6 624 30 15146183
  48. [54]Burda P Vargova J Curik N Salek C Papadopoulos GL Strouboulis J GATA-1 Inhibits PU.1 Gene via DNA and Histone H3K9 Methylation of Its Distal Enhancer in Erythroleukemia PLoS One 2016 11 3 e0152234 27010793 PMC4807078
  49. [55]Curik N Burda P Vargova K Pospisil V Belickova M Vlckova P 5-azacitidine in aggressive myelodysplastic syndromes regulates chromatin structure at PU.1 gene and cell differentiation capacity Leukemia 2012 26 8 1804 11 22343522
  50. [56]Rose D Haferlach T Schnittger S Perglerova K Kern W Haferlach C Subtype-specific patterns of molecular mutations in acute myeloid leukemia Leukemia 2017 31 1 11 7 27285584
  51. [57]Shen J Sheng X Chang Z Wu Q Wang S Xuan Z Iron metabolism regulates p53 signaling through direct heme-p53 interaction and modulation of p53 localization, stability, and function Cell Rep 2014 7 1 180 93 24685134 PMC4219651
  52. [58]Trainor CD Mas C Archambault P Di Lello P Omichinski JG GATA-1 associates with and inhibits p53 Blood 2009 114 1 165 73 19411634 PMC2710945
  53. [59]Shimizu R Engel JD Yamamoto M GATA1-related leukaemias Nat Rev Cancer 2008 8 4 279 87 18354416
  54. [60]Crispino JD GATA1 in normal and malignant hematopoiesis Semin Cell Dev Biol 2005 16 1 137 47 15659348
  55. [62]Prinjha RK Witherington J Lee K Place your BETs: the therapeutic potential of bromodomains Trends Pharmacol Sci 2012 33 3 146 53 22277300
  56. [63]Zuber J Shi J Wang E Rappaport AR Herrmann H Sison EA RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia Nature 2011 478 7370 524 8 21814200 PMC3328300
  57. [64]Goupille O Penglong T Lefevre C Granger M Kadri Z Fucharoen S BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7 Biochem Biophys Res Commun 2012 429 1–2 1 5 23137537
  58. [65]Osawa M Yamaguchi T Nakamura Y Kaneko S Onodera M Sawada K Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis Blood 2002 100 8 2769 77 12351384
  59. [66]Elmaagacli AH Koldehoff M Zakrzewski JL Steckel NK Ottinger H Beelen DW Growth factor-independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate Br J Haematol 2007 136 2 212 9 17156408
  60. [67]Kubota A Okamura S Shimoda K Ikematsu W Otsuka T Niho Y Analysis of c-kit expression of human erythroleukemia cell line, HEL: clonal variation and relationship with erythroid and megakaryocytic phenotype Leuk Res 1995 19 4 283 90 7538619
  61. [68]Felli N Fontana L Pelosi E Botta R Bonci D Facchiano F MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation Proc Natl Acad Sci U S A 2005 102 50 18081 6 16330772 PMC1312381
  62. [69]Kuvardina ON Herglotz J Kolodziej S Kohrs N Herkt S Wojcik B RUNX1 represses the erythroid gene expression program during megakaryocytic differentiation Blood 2015 125 23 3570 9 25911237 PMC4463808
  63. [70]Wickrema A Crispino JD Erythroid and megakaryocytic transformation Oncogene 2007 26 47 6803 15 17934487
  64. [71]Thomas SJ Snowden JA Zeidler MP Danson SJ The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours Br J Cancer 2015 113 3 365 71 26151455 PMC4522639
  65. [72]Kirito K Nagashima T Ozawa K Komatsu N Constitutive activation of Stat1 and Stat3 in primary erythroleukemia cells Int J Hematol 2002 75 1 51 4 11843291
  66. [73]Hegde S Ni S He S Yoon D Feng GS Watowich SS Stat3 promotes the development of erythroleukemia by inducing Pu.1 expression and inhibiting erythroid differentiation Oncogene 2009 28 38 3349 59 19581930 PMC3086737
  67. [74]Iwatsuki K Endo T Misawa H Yokouchi M Matsumoto A Ohtsubo M STAT5 activation correlates with erythropoietin receptor-mediated erythroid differentiation of an erythroleukemia cell line J Biol Chem 1997 272 13 8149 52 9079629
  68. [76]Moreau-Gachelin F Multi-stage Friend murine erythroleukemia: molecular insights into oncogenic cooperation Retrovirology 2008 5 99 18983647 PMC2585586
  69. [77]Calin GA Ferracin M Cimmino A Di Leva G Shimizu M Wojcik SE A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia N Engl J Med 2005 353 17 1793 801 16251535
  70. [78]Zhan M Miller CP Papayannopoulou T Stamatoyannopoulos G Song CZ MicroRNA expression dynamics during murine and human erythroid differentiation Exp Hematol 2007 35 7 1015 25 17588470 PMC1955220
  71. [79]Bruchova-Votavova H Yoon D Prchal JT miR-451 enhances erythroid differentiation in K562 cells Leuk Lymphoma 2010 51 4 686 93 20218812
  72. [80]Su R Dong L Zou D Zhao H Ren Y Li F microRNA-23a, -27a and -24 synergistically regulate JAK1/Stat3 cascade and serve as novel therapeutic targets in human acute erythroid le ukemia Oncogene 2016 35 46 6001 14 27086927
  73. [81]Grossmann V Bacher U Haferlach C Schnittger S Potzinger F Weissmann S Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics Leukemia 2013 27 9 1940 3 23648669
  74. [82]Cervera N Carbuccia N Garnier S Guille A Adelaide J Murati A Molecular characterization of acute erythroid leukemia (M6-AML) using targeted next-generation sequencing Leukemia 2016 30 4 966 70 26202927
  75. [84]Micci F Thorsen J Panagopoulos I Nyquist KB Zeller B Tierens A High-throughput sequencing identifies an NFIA/CBFA2T3 fusion gene in acute erythroid leukemia with t(1;16)(p31;q24) Leukemia 2013 27 4 980 2 23032695 PMC3626019
  76. [85]Panagopoulos I Micci F Thorsen J Haugom L Buechner J Kerndrup G Fusion of ZMYND8 and RELA genes in acute erythroid leukemia PLoS One 2013 8 5 e63663 23667654 PMC3646816
  77. [86]DeAngelo DJ Stein EM Ravandi F Evolving Therapies in Acute Myeloid Leukemia: Progress at Last? Am Soc Clin Oncol Educ Book 2016 35 e302 12 27249736
  78. [87]Vicente C Conchillo A Garcia-Sanchez MA Odero MD The role of the GATA2 transcription factor in normal and malignant hematopoiesis Crit Rev Oncol Hematol 2012 82 1 1 17 21605981

Cited by

Sorted by citations

Authors
Boddu, P., Benton, C. B., Wang, W., Borthakur, G., Khoury, J. D., & Pemmaraju, N.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
  • Khoury, Joseph D.
  • Pemmaraju, Naveen
ORCID
Venue
Blood Reviews
Publisher
Elsevier BV
Published
2018-03
Volume
32
Issue
2
Pages
96-105
ISSN
0268-960X (ISSN-L)
DOI
10.1016/j.blre.2017.09.002
PMC
PMC5857409
OpenAlex
W2754059711
Cited by
49
References
5
Citations by year
2026: 4 · 2025: 4 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 8
FWCI
0.60
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Blood Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
MD Anderson Cancer Center (CA016672, P01 CA049639)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
Keywords
erythroleukemia, acute myeloid leukemia, erythroid lineage, molecular characterization, therapeutic target, diagnosis, prognosis, pathophysiology
MeSH terms
Animals, Biopsy, Bone Marrow, Leukemia, Erythroblastic, Acute, Humans, Prognosis, Signal Transduction, Gene Expression Regulation, Leukemic, Practice Guidelines as Topic, Disease Management

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