ГОСТРІ МІЄЛОЇДНІ ЛЕЙКЕМІЇ У П’ЯТОМУ ПЕРЕГЛЯДІ КЛАСИФІКАЦІЇ ВООЗ ГЕМАТОЛІМФОЇДНИХ ПУХЛИН (Частина 1)
DOI:
https://doi.org/10.15407/oncology.2025.02.085Ключові слова:
Всесвітня організація охорони здоров’я, класифікація, гострі лейкемії, мієлоїдні новоутворення, діагностичні критерії, імунофенотипування, прогноз захворюванняАнотація
У 2022 р. фахівцями ВООЗ було запропоноване чергове 5-те видання класифікації гематолімфоїдних пухлин (ВООЗ-ГЛП5), яке стало суттєвим оновленням попереднього “Переглянутого 4-го видання класифікації ВООЗ пухлин кровотворної та лімфоїдної тканин”. У 2024 р. основи класифікації ВООЗ-ГЛП5 були викладені у 11-му томі відповідної серії монографій ВООЗ для класифікації пухлин людини (також відомої як “Сині книги” ВООЗ), які публікуються Міжнародною агенцією з вивчення раку. В огляді, що складається із двох частин, представлено характеристику основних форм гострих мієлоїдних лейкемій (ГМЛ), які увійшли до ВООЗ-ГЛП5. Головну увагу зосереджено на уточнених критеріях лабораторної діагностики ГМЛ та прогностичному значенні цитогенетичних аномалій, мутацій або перебудов генів при окремих формах ГМЛ. Першу частину присвячено аналізу ГМЛ з визначальними генетичними аномаліями, тоді як ГМЛ, які вирізняються за рівнем диференціювання, мієлоїдна саркома, мієлоїдні новоутворення після застосування цитотоксичної терапії, мієлоїдні новоутворення, пов’язані зі схильністю на рівні зародкової лінії та новоутворення з плазмоцитоїдних дендритних клітин, будуть розглянуті у другій частині огляду.
Посилання
Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classifi ation of Haematolym- phoid Tumours: Myeloid and histiocytic/dendritic neo- plasms. Leukemia 2022; 36 (7): 1703–19. https://doi.org/ 10.1038/s41375-022-01613-1.
Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edi- tion of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid neoplasms. Leuke- mia 2022; 36 (7): 1720–48. https://doi.org/10.1038/s41375- 022-01620-2.
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127 (20): 2375–90. https://doi. org/10.1182/blood-2016-01-643569.
Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127 (20): 2391– 405. https://doi.org/10.1182/blood-2016-03-643544.
Haematolymphoid Tumours. WHO Classifi ation of Tu- mours, 5th Edition, Volume 11. Edited by the WHO Clas- sification of Tumours Editorial Board. Lyon: IARC, 2024. 958 p. ISBN-13: 978-92-832-4520-9.
Arber DA, Orazi A, Hasserjian RP, et al. International Con- sensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating morphologic, clinical, and geno- mic data. Blood 2022; 140 (11): 1200–28. https://doi.org/ 10.1182/blood.2022015850.
Campo E, Jaffe ES, Cook JR, et al. The International Con- sensus Classification of Mature Lymphoid Neoplasms: A report from the Clinical Advisory Committee. Blood 2022; 140 (11): 1229–53. https://doi.org/10.1182/blood. 2022015851.
SEER Cancer Stat Facts: Acute Myeloid Leukemia. National Cancer Institute. Bethesda, MD. Available from: https:// seer.cancer.gov/statfacts/html/amyl.html.
Juliusson G, Lehmann S, Lazarevic М. Epidemiology and etiology of AML. In: C Röllig, GJ Ossenkoppele (eds.), Acute Myeloid Leukemia, Hematologic Malignancies, Springer Nature Switzerland AG, 2021: 1–22. https://doi. org/10.1007/978-3-030-72676-8_1.
Koval SV, Gluzman DF, Sklyarenko LM, et al. Hematological malignancies in Ukraine in post-Chernobyl era: Sources of data and their preliminary analysis. Ann Hematol 2020; 99 (7): 1543–50. https://doi.org/10.1007/s00277-020- 04076-5.
Zhang MY, Othus M, McMillen K, et al. Association between class III obesity and overall survival in previously untreated younger patients with acute myeloid leukemia enrolled on SWOG S1203. Leukemia 2024; 38 (7): 1488–93. https:// doi.org/10.1038/s41375-024-02288-6.
Philchenkov AA, Zavelevich MP, Abramenko IV. B-cell lym- phoid neoplasms in the 5th edition of the WHO Classi- fication of Hematolymphoid Tumors (2022). 1. General principles of classification. Precursor B-cell neoplasms. Oncology 2023; 25 (2): 89–103. https://doi.org/10.15407/ oncology.2023.02.089 (in Ukrainian).
Philchenkov AA, Zavelevich MP, Abramenko IV, et al. B-cell lymphoid neoplasms in the 5th edition of the WHO Clas- sification of Hematolymphoid Tumors (2022). 2. Mature B-cell neoplasms, plasma cell neoplasms and other diseases with paraproteins. Oncology 2023; 25 (3): 159–74. https:// doi.org/10.15407/oncology.2023.03.159 (in Ukrainian).
Philchenkov AA, Abramenko IV, Zavelevich MP. Myelo- dysplastic neoplasms/syndromes in the 5th edition of the WHO Classification of Hematolymphoid Tumors (2022). Oncology 2024; 26 (4): 235–48. https://doi.org/10.15407/ oncology.2024.04.235 (in Ukrainian).
Lallemand-Breitenbach V, de Thé H. PML nuclear bod- ies. Cold Spring Harb Perspect Biol 2010; 2 (5): a000661. https://doi.org/10.1101/cshperspect.a000661.
Liquori A, Ibañez M, Sargas C, et al. Acute promyelocytic leukemia: A constellation of molecular events around a single PML-RARA fusion gene. Cancers (Basel) 2020; 12 (3): 624. https://doi.org/10.3390/cancers12030624.
Zhu J, Gianni M, Kopf E, et al. Retinoic acid induces protea- some-dependent degradation of retinoic acid receptor alpha (RARalpha) and oncogenic RARalpha fusion proteins. Proc Natl Acad Sci USA 1999; 96 (26): 14807–12. https://doi. org/10.1073/pnas.96.26.14807.
Lallemand-Breitenbach V, Jeanne M, Benhenda S, et al. Ar- senic degrades PML or PML-RARalpha through a SUMO- triggered RNF4/ubiquitin-mediated pathway. Nat Cell Biol 2008; 10 (5): 547–55. https://doi.org/10.1038/ncb1717.
Iland HJ, Collins M, Bradstock K, et al. Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leu- kaemia and Lymphoma Group (ALLG) APML4 study: A non-randomised phase 2 trial. Lancet Haematol 2015; 2 (9): e357–66. https://doi.org/10.1016/S2352-3026(15) 00115-5.
Park JH, Qiao B, Panageas KS, et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood 2011; 118 (5): 1248–54. https://doi. org/10.1182/blood-2011-04-346437.
Sanz MA, Fenaux P, Tallman MS, et al. Management of acute promyelocytic leukemia: Updated recommendations from an expert panel of the European LeukemiaNet. Blood 2019; 133 (15): 1630–43. https://doi.org/10.1182/blood- 2019-01-894980.
Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022; 140 (12): 1345–77. https://doi.org/10.1182/ blood.2022016867.
Fang H, Wang SA, Hu S, et al. Acute promyelocytic leuke- mia: Immunophenotype and differential diagnosis by flow cytometry. Cytometry B Clin Cytom 2022; 102 (4): 283–91. https://doi.org/10.1002/cyto.b.22085.
Sainty D, Liso V, Cantù-Rajnoldi A, et al. A new morpho- logic classification system for acute promyelocytic leu- kemia distinguishes cases with underlying PLZF/RARA gene rearrangements. Blood 2000; 96 (4): 1287–96. PMID: 10942370.
Horna P, Zhang L, Sotomayor EM, et al. Diagnostic im- munophenotype of acute promyelocytic leukemia before and early during therapy with all-trans retinoic acid. Am J Clin Pathol 2014; 142 (4): 546–52. https://doi.org/10.1309/ AJCPPOKEHBP53ZHV
Shang L, Chen X, Liu Y, et al. The immunophenotypic characteristics and flow cytometric scoring system of acute myeloid leukemia with t(8;21)(q22;q22); RUNX1- RUNX1T1. Int J Lab Hematol 2019; 41 (1): 23–31. https:// doi.org/10.1111/ij 12916.
Sameeta F, Wang SA, Tang Z, et al. Integrative immuno- phenotypic and genetic characterization of acute myeloid leukemia with CBFB rearrangement. Am J Clin Pathol 2024; 162 (5): 455–63. https://doi.org/10.1093/ajcp/ aqae060.
Hoff ter LM, Orhan E, Walter C, et al. Impact of KMT2A rearrangement and CSPG4 expression in pediatric acute myeloid leukemia. Cancers (Basel) 2021; 13 (19): 4817. https://doi.org/10.3390/cancers13194817.
Suzuki T, Kiyoi H, Ozeki K, et al. Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia. Blood 2005; 106 (8): 2854–61. https:// doi.org/10.1182/blood-2005-04-1733.
Liu Q, Qi L, Yang M, et al. Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia. Int J Lab Hematol 2023; 45 (5): 743–50. https://doi.org/10.1111/ ij 14124.
Reikvam H, Hatfi KJ, Kittang AO, et al. Acute myeloid leukemia with the t(8;21) translocation: Clinical conse- quences and biological implications. J Biomed Biotechnol 2011; 2011: 104631. https://doi.org/10.1155/2011/104631.
Brettingham-Moore KH, Taberlay PC, Holloway AF. Inter- play between transcription factors and the epigenome: In- sight from the role of RUNX1 in leukemia. Front Immunol 2015; 6: 499. https://doi.org/10.3389/fi 15.00499.
Swart LE, Heidenreich O. The RUNX1/RUNX1T1 net- work: Translating insights into therapeutic options. Exp Hematol 2021; 94: 1–10. https://doi.org/10.1016/j.exphem. 2020.11.005.
Higuchi A, Iriyama N. RUNX1::RUNX1T1 acute myeloid leukemia cytogenetically showing t(6;8)(p23;q22). Cureus 2024; 16 (3): e56342. https://doi.org/10.7759/cureus. 56342.
Gudipati M, Butler M, Koka R, et al. Fusion gene-based classification of variant cytogenetic rearrangements in acute myeloid leukemia. Genes (Basel) 2023; 14 (2): 396. https:// doi.org/10.3390/genes14020396.
Menter T, Lundberg P, Wenzel F, et al. RUNX1 mutations can lead to aberrant expression of CD79a and PAX5 in acute myelogenous leukemias: A potential diagnostic pit- fall. Pathobiology 2019; 86 (2–3): 162–166. https://doi. org/10.1159/000493688.
Ishikawa Y, Kawashima N, Atsuta Y, et al. Prospective evalu- ation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11. Blood Adv 2020; 4 (1): 66–75. https://doi.org/10.1182/bloodadvances.2019000709.
Haferlach T, Winkemann M, Löffler H, et al. The abnormal eosinophils are part of the leukemic cell population in acute myelomonocytic leukemia with abnormal eosinophils (AML M4Eo) and carry the pericentric inversion 16: A combina- tion of May-Grünwald-Giemsa staining and fluorescence in situ hybridization. Blood 1996; 87 (6): 2459–63. PMID: 8630411.
Shigesada K, van de Sluis B, Liu PP. Mechanism of leuke- mogenesis by the inv(16) chimeric gene CBFB/PEBP2B- MHY11. Oncogene 2004; 23 (24): 4297–307. https://doi. org/10.1038/sj.onc.1207748.
Schwind S, Edwards CG, Nicolet D, et al. inv(16)/t(16;16) acute myeloid leukemia with non-type A CBFB-MYH11 fusions associate with distinct clinical and genetic features and lack KIT mutations. Blood 2013; 121 (2): 385–91. https://doi.org/10.1182/blood-2012-07-442772.
Appelbaum FR, Kopecky KJ, Tallman MS, et al. The clini- cal spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. Br J Haematol 2006; 135 (2): 165–73. https://doi.org/10.1111/j.1365-2141. 2006.06276.x.
Billström R, Ahlgren T, Békássy AN, et al. Acute myeloid leukemia with inv(16)(p13q22): Involvement of cervical lymph nodes and tonsils is common and may be a negative prognostic sign. Am J Hematol 2002; 71 (1): 15–9. https:// doi.org/10.1002/ajh.10170.
Bain BJ, Béné MC. Morphological and immunopheno- typic clues to the WHO categories of acute myeloid leu- kaemia. Acta Haematol 2019; 141 (4): 232–44. https:// doi.org/10.1159/000496097
Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommenda- tions from an international expert panel. Blood 2017; 129: 424–48. https://doi.org/10.1182/blood-2016-08-733196.
Talami A, Bettelli F, Pioli V, et al. How to improve prognos- tication in acute myeloid leukemia with CBFB-MYH11 fu- sion transcript: Focus on the role of molecular measurable residual disease (MRD) monitoring. Biomedicines 2021; 9 (8): 953. https://doi.org/10.3390/biomedicines9080953.
Oyarzo MP, Lin P, Glassman A, et al. Acute myeloid leuke- mia with t(6;9)(p23;q34) is associated with dysplasia and a high frequency of FLT3 gene mutations. Am J Clin Pathol 2004; 122 (3): 348–58. https://doi.org/10.1309/5DGB- 59KQ-A527-PD47.
Potluri S, Kellaway SG, Coleman DJL, et al. Gene regula- tion in t(6;9) DEK::NUP214 Acute Myeloid Leukemia re- sembles that of FLT3-ITD/NPM1 Acute Myeloid Leukemia but with an altered HOX/MEIS axis. Leukemia 2024; 38 (2): 403–7. https://doi.org/10.1038/s41375-023-02118-1.
Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-ac- tivating mutations in 979 patients with acute myelogenous leukemia: Association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002; 99 (12): 4326–35. https://doi.org/10.1182/blood.v99.12.4326.
Csizmar CM, Saliba AN, Greipp PT, et al. FLT3 inhibitors potentially improve response rates in acute myeloid leuke- mia harboring t(6;9)(DEK::NUP214): The Mayo Clinic experience. Haematologica 2024; 109 (11): 3785–9. https:// doi.org/10.3324/haematol.2024.285359.
Ma Z, Morris SW, Valentine V, et al. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 2001; 28 (3): 220–1. https://doi.org/10.1038/90054.
Patil DP, Chen CK, Pickering BF, et al. m(6)A RNA methy- lation promotes XIST-mediated transcriptional repression. Nature 2016; 537 (7620): 369–73. https://doi.org/10.1038/ nature19342.
Reed F, Larsuel ST, Mayday MY, et al. MRTFA: A critical protein in normal and malignant hematopoiesis and beyond. J Biol Chem 2021; 296: 100543. https://doi.org/10.1016/j. jbc.2021.100543.
Gruber TA, Downing JR. The biology of pediatric acute megakaryoblastic leukemia. Blood 2015; 126 (8): 943–9. https://doi.org/10.1182/blood-2015-05-567859.
Carroll A, Civin C, Schneider N, et al. The t(1;22) (p13;q13) is nonrandom and restricted to infants with acute mega- karyoblastic leukemia: A Pediatric Oncology Group Study. Blood 1991; 78 (3): 748–52. PMID: 1859887.
Bernstein J, Dastugue N, Haas OA, et al. Nineteen cases of the t(1;22)(p13;q13) acute megakaryblastic leukaemia of infants/children and a review of 39 cases: Report from a t(1;22) study group. Leukemia 2000; 14 (1): 216–8. https:// doi.org/10.1038/sj.leu.2401639.
Chisholm KM, Smith J, Heerema-McKenney AE, et al. Pathologic, cytogenetic, and molecular features of acute myeloid leukemia with megakaryocytic differentiation: A report from the Children’s Oncology Group. Pediatr Blood Cancer 2023; 70 (5): e30251. https://doi.org/10.1002/ pbc.30251.
Cuneo A, Balboni M, Piva N, et al. Lineage switch and mul- tilineage involvement in two cases of pH chromosome- positive acute leukemia: Evidence for a stem cell disease. Haematologica 1994; 79 (1): 76–82. PMID: 15378954.
Grimwade D, Hills RK, Moorman AV, et al. 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 2010; 116 (3): 354–65. https://doi. org/10.1182/blood-2009-11-254441.
Soupir CP, Vergilio JA, Dal Cin P, et al. Philadelphia chro- mosome-positive acute myeloid leukemia: A rare aggres- sive leukemia with clinicopathologic features distinct from chronic myeloid leukemia in myeloid blast crisis. Am J Clin Pathol 2007; 127 (4): 642–50. https://doi.org/10.1309/ B4NVER1AJJ84CTUU.
Mizuno S, Takami A, Kawamura K, et al. Allogeneic he- matopoietic cell transplantation for acute myeloid leukemia with BCR::ABL1 fusion. EJHaem 2024; 5 (2): 369–78. https://doi.org/10.1002/jha2.877.
Piedimonte M, Ottone T, Alfonso V, et al. A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: Case report and literature review. BMC Cancer 2019; 19 (1): 50. https://doi.org/10.1186/s12885-019-5265-5.
Mitelman F. The cytogenetic scenario of chronic myeloid leukemia. Leuk Lymphoma 1993; 11 (Suppl 1): 11–5. https://doi.org/10.3109/10428199309047856.
Nacheva EP, Grace CD, Brazma D, et al. Does BCR/ABL1 positive acute myeloid leukaemia exist? Br J Haematol 2013; 161 (4): 541–50. https://doi.org/10.1111/bjh.12301.
Nacheva EP, Brazma D, Virgili A, et al. Deletions of immu- noglobulin heavy chain and T cell receptor gene regions are uniquely associated with lymphoid blast transformation of chronic myeloid leukemia. BMC Genomics 2010; 11: 41. https://doi.org/10.1186/1471-2164-11-41.
Low SK, Nanua S, Patel M, et al. AML with BCR-ABL1 fusion treated with imatinib, a hypomethylating agent and venetoclax. Leuk Res Rep 2022; 17: 00333. https://doi. org/10.1016/j.lrr.2022.100333.
Han E, Lee H, Kim M, et al. Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16) chromo- somal abnormalities. Blood Res 2014; 49 (1): 22–8. https:// doi.org/10.5045/br.2014.49.1.22.
Vitale C, Lu X, Abderrahman B, et al. t(9;22) as secondary alteration in core-binding factor de novo acute myeloid leukemia. Am J Hematol 2015; 90 (11): E211–2. https:// doi.org/10.1002/ajh.24143.
Shilatifard A. The COMPASS family of histone H3K4 methy- lases: mechanisms of regulation in development and disease pathogenesis. Annu Rev Biochem 2012; 81: 65–95. https:// doi.org/10.1146/annurev-biochem-051710-134100.
Meyer C, Larghero P, Almeida Lopes B, et al. The KMT2A recombinome of acute leukemias in 2023. Leukemia 2023; 37 (5): 988–1005. https://doi.org/10.1038/s41375-023- 01877-1.
Schoch C, Schnittger S, Klaus M, et al. AML with 11q23/ MLL abnormalities as defined by the WHO classification: Incidence, partner chromosomes, FAB subtype, age dis- tribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. Blood 2003; 102 (7): 2395–402. https://doi.org/10.1182/blood-2003- 02-0434.
Meyer C, Burmeister T, Gröger D, et al. The MLL recombi- nome of acute leukemias in 2017. Leukemia 2018; 32 (2): 273–84. https://doi.org/10.1038/leu.2017.213.
de Rooij JDE, Branstetter C, Ma J, et al. Pediatric non- Down syndrome acute megakaryoblastic leukemia is charac- terized by distinct genomic subsets with varying outcomes. Nat Genet 2017; 49 (3): 451–6. https://doi.org/10.1038/ ng.3772.
Hara Y, Shiba N, Ohki K, et al. Prognostic impact of spe- cifi molecular profi in pediatric acute megakaryoblastic leukemia in non-Down syndrome. Genes Chromosomes Cancer 2017; 56 (5): 394–404. https://doi.org/10.1002/ gcc.22444.
Bill M, Mrózek K, Kohlschmidt J, et al. Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/KMT2A. Proc Natl Acad Sci USA 2020; 117 (42): 26340–6. https:// doi.org/10.1073/pnas.2014732117.
Vetro C, Haferlach T, Meggendorfer M, et al. Cytogenetic and molecular genetic characterization of KMT2A-PTD posi- tive acute myeloid leukemia in comparison to KMT2A-re- arranged acute myeloid leukemia. Cancer Genet 2020; 240: 15–22. https://doi.org/10.1016/j.cancergen.2019.10.006.
Tong J, Zhang L, Liu H, et al. Umbilical cord blood trans- plantation can overcome the poor prognosis of KMT2A- MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival. Ann Hematol 2021; 100 (5): 1303–9. https://doi.org/10.1007/s00277-021- 04413-2.
Guarnera L, D’Addona M, Bravo-Perez C, et al. KMT2A rearrangements in leukemias: Molecular aspects and ther- apeutic perspectives. Int J Mol Sci 2024; 25 (16): 9023. https://doi.org/10.3390/ij169023.
Candoni A, Coppola G. A 2024 update on menin inhibitors. A new class of target agents against KMT2A-rearranged and NPM1-mutated acute myeloid leukemia. Hematol Rep 2024; 16 (2): 244–54. https://doi.org/10.3390/hematol- rep16020024.
Chakraborty S, Senyuk V, Sitailo S, et al. Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-locali- zation in nuclear speckles. J Biol Chem 2001; 276 (48): 44936–43. https://doi.org/10.1074/jbc.M106733200.
Liu K, Tirado CA. MECOM: A very interesting gene involved also in lymphoid malignancies. J Assoc Genet Technol 2019; 45 (3): 109–14. PMID: 31554743.
Medeiros BC, Kohrt HE, Arber DA, et al. Immunophe- notypic features of acute myeloid leukemia with inv(3) (q21q26.2)/t(3;3)(q21;q26.2). Leuk Res 2010; 34 (5): 594–7.
https://doi.org/10.1016/j.leukres.2009.08.029.
Yamamoto K, Okamura A, Sanada Y, et al. Marked throm- bocytosis and dysmegakaryopoiesis in acute myeloid leuke- mia with t(2;3)(p22;q26.2) and EVI1 rearrangement. Ann Hematol 2013; 92 (12): 1713–5. https://doi.org/10.1007/ s00277-013-1750-0.
Gröschel S, Sanders MA, Hoogenboezem R, et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell 2014; 157 (2): 369–81. https://doi.org/10.1016/j.cell.2014.02.019.
Tang Z, Wang W, Yang S, et al. 3q26.2/MECOM rearrange- ments by pericentric inv(3): Diagnostic challenges and clinicopathologic features. Cancers (Basel) 2023; 15 (2): 458. https://doi.org/10.3390/cancers15020458.
De Braekeleer E, Douet-Guilbert N, Basinko A, et al. Con- ventional cytogenetics and breakpoint distribution by fl o- rescent in situ hybridization in patients with malignant hemopathies associated with inv(3)(q21;q26) and t(3;3) (q21;q26). Anticancer Res 2011; 31 (10): 3441–8. PMID: 21965759.
Gröschel S, Sanders MA, Hoogenboezem R, et al. Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling path- ways. Blood 2015; 125 (1): 133–9. https://doi.org/10.1182/ blood-2014-07-591461.
Summerer I, Haferlach C, Meggendorfer M, et al. Prognosis of MECOM (EVI1)-rearranged MDS and AML patients rather depends on accompanying molecular mutations than on blast count. Leuk Lymphoma 2020; 61 (7): 1756–9. https://doi.org/10.1080/10428194.2020.1737689.
Halaburda K, Labopin M, Houhou M, et al. AlloHSCT for inv(3)(q21;q26)/t(3;3)(q21;q26) AML: A report from the acute leukemia working party of the European society for blood and marrow transplantation. Bone Marrow Trans- plant 2018; 53 (6): 683–91. https://doi.org/10.1038/s41409- 018-0165-x.
Gao J, Gurbuxani S, Zak T, et al. Comparison of myeloid neoplasms with nonclassic 3q26.2/MECOM versus classic inv(3)/t(3;3) rearrangements reveals diverse clinicopatho- logic features, genetic profiles, and molecular mechanisms of MECOM activation. Genes Chromosomes Cancer 2022; 61 (2): 71–80. https://doi.org/10.1002/gcc.23004.
Struski S, Lagarde S, Bories P, et al. NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecu- lar homogenous group with a poor prognosis. Leukemia 2017; 31 (3): 565–72. https://doi.org/10.1038/leu.2016. 267.
Rasouli M, Troester S, Grebien F, et al. NUP98 oncofu- sions in myeloid malignancies: An update on molecular mechanisms and therapeutic opportunities. Hemasphere 2024; 8 (9): e70013. https://doi.org/10.1002/hem3.70013.
Fontoura BM, Blobel G, Matunis MJ. A conserved biogen- esis pathway for nucleoporins: Proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96. J Cell Biol 1999; 144 (6): 1097–112. https://doi.org/10.1083/jcb.144.6.1097.
Michmerhuizen NL, Klco JM, Mullighan CG. Mechanistic insights and potential therapeutic approaches for NUP98- rearranged hematologic malignancies. Blood 2020; 136 (20): 2275–89. https://doi.org/10.1182/blood.2020007093.
Gough SM, Slape CI, Aplan PD. NUP98 gene fusions and hematopoietic malignancies: Common themes and new biologic insights. Blood 2011; 118 (24): 6247–57. https:// doi.org/10.1182/blood-2011-07-328880.
Mohanty S. NUP98 rearrangements in AML: Molecular mechanisms and clinical implications. Onco 2023; 3: 147– 64. https://doi.org/10.3390/onco3030011.
Hollink IH, van den Heuvel-Eibrink MM, Arentsen-Peters ST, et al. NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern. Blood 2011; 118 (13): 3645–56. https:// doi.org/10.1182/blood-2011-04-346643.
Zhu HH, Yang MC, Wang F, et al. Identification of a novel NUP98-RARA fusion transcript as the 14th variant of acute promyelocytic leukemia. Am J Hematol 2020; 95 (7): E184–6. https://doi.org/10.1002/ajh.25807
Cheng CK, Chan HY, Yung YL, et al. A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia. Blood Adv 2022; 6 (2): 410–5. https://doi.org/10.1182/bloodadvances.2021006064.
Such E, Cervera J, Valencia A, et al. A novel NUP98/RARG gene fusion in acute myeloid leukemia resembling acute pro- myelocytic leukemia. Blood 2011; 117 (1): 242–5. https:// doi.org/10.1182/blood-2010-06-291658.
de Rooij JD, Masetti R, van den Heuvel-Eibrink MM, et al. Recurrent abnormalities can be used for risk group stratifi- cation in pediatric AMKL: A retrospective intergroup study. Blood 2016; 127 (26): 3424–30. https://doi.org/10.1182/ blood-2016-01-695551.
Bertrums EJM, Smith JL, Harmon L, et al. Comprehen- sive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia. Haemato- logica 2023; 108 (8): 2044–58. https://doi.org/10.3324/ haematol.2022.281653.
Niktoreh N, Walter C, Zimmermann M, et al. Mutated WT1, FLT3-ITD, and NUP98-NSD1 fusion in various combi- nations define a poor prognostic group in pediatric acute myeloid leukemia. J Oncol 2019; 2019: 1609128. https:// doi.org/10.1155/2019/1609128.
Ostronoff F, Othus M, Gerbing RB, et al. NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: A COG and SWOG report. Blood 2014; 124 (15): 2400–7. https://doi. org/10.1182/blood-2014-04-570929.
Pommert L, Tarlock K. The evolution of targeted therapy in pediatric AML: Gemtuzumab ozogamicin, FLT3/IDH/ BCL2 inhibitors, and other therapies. Hematology Am Soc Hematol Educ Program 2022; 2022 (1): 603–10. https:// doi.org/10.1182/hematology.2022000358.
Perner F, Stein EM, Wenge DV, et al. MEN1 mutations mediate clinical resistance to menin inhibition. Nature 2023; 615 (7954): 913–9. https://doi.org/10.1038/s41586- 023-05755-9.
Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleo- phosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005; 352 (3): 254–66. https:// doi.org/10.1056/NEJMoa041974.
Yu Y, Maggi LB, Brady SN, et al. Nucleophosmin is es- sential for ribosomal protein L5 nuclear export. Mol Cell Biol 2006; 26 (10): 3798–809. https://doi.org/10.1128/ MCB.26.10.3798-3809.2006.
Okuda M, Horn HF, Tarapore P, et al. Nucleophosmin/ B23 is a target of CDK2/cyclin E in centrosome duplica- tion. Cell 2000; 103 (1): 127–40. https://doi.org/10.1016/ S0092-8674(00)00093-3.
Colombo E, Marine JC, Danovi D, et al. Nucleophosmin regulates the stability and transcriptional activity of p53. Nat Cell Biol 2002; 4 (7): 529–33. https://doi.org/10.1038/ ncb814.
Falini B, Brunetti L. Sportoletti P, et al. NPM1-mutated acute myeloid leukemia: From bench to bedside. Blood 2020; 136 (15): 1707–21. https://doi.org/10.1182/blood. 2019004226.
Alpermann T, Schnittger S, Eder C, et al. Molecular sub- types of NPM1 mutations have diff rent clinical profi specifi patterns of accompanying molecular mutations and varying outcomes in intermediate risk acute myeloid leukemia. Haematologica 2016; 101 (2): e55–8. https:// doi.org/10.3324/haematol.2015.133819.
Stade K, Ford CS, Guthrie C, et al. Exportin 1 (Crm1p) is an essential nuclear export factor. Cell 1997; 90 (6): 1041– 50. https://doi.org/10.1016/s0092-8674(00)80370-0.
Thiede C, Koch S, Creutzig E, et al. Prevalence and prog- nostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood 2006; 107 (10): 4011–20. https://doi.org/10.1182/blood-2005-08-3167.
Bain BJ, Heller M, Toma S, et al. The cytological features of NPM1-mutated acute myeloid leukemia. Am J Hematol 2015; 90 (6): 560. https://doi.org/10.1002/ajh.24002.
Matarraz S, Leoz P, Yeguas-Bermejo A, et al. Baseline immunophenotypic profi of bone marrow leukemia cells in acute myeloid leukemia with nucleophosmin-1 gene mutation: A EuroFlow study. Blood Cancer J 2023; 13 (1): 132. https://doi.org/10.1038/s41408-023-00909-4.
Straube J, Ling VY, Hill GR, et al. The impact of age, NPM1mut, and FLT3ITD allelic ratio in patients with acute myeloid leukemia. Blood 2018; 131 (10): 1148–53. https:// doi.org/10.1182/blood-2017-09-807438.
Li J, Zhang X, Sejas DP, et al. Negative regulation of p53 by nucleophosmin antagonizes stress-induced apoptosis in human normal and malignant hematopoietic cells. Leuk Res 2005; 29 (12): 1415–23. https://doi.org/10.1016/j.leukres. 2005.05.005.
Choudhary C, Schwäble J, Brandts C, et al. AML-associated Flt3 kinase domain mutations show signal transduction dif- ferences compared with Flt3 ITD mutations. Blood 2005; 106 (1): 265–73. https://doi.org/10.1182/blood-2004-07- 2942.
Gaidzik VI, Weber D, Paschka P, et al. DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia. Leuke- mia 2018; 32 (1): 30–7. https://doi.org/10.1038/leu.2017. 200.
Bezerra MF, Lima AS, Piqué-Borràs MR, et al. Co-oc- currence of DNMT3A, NPM1, FLT3 mutations identifi a subset of acute myeloid leukemia with adverse progno- sis. Blood 2020; 135 (11): 870–5. https://doi.org/10.1182/
blood.2019003339.
Angenendt L, Röllig C, Montesinos P, et al. Chromosomal abnormalities and prognosis in NPM1-mutated acute mye- loid leukemia: A pooled analysis of individual patient data from nine international cohorts. J Clin Oncol 2019; 37 (29): 2632–42. https://doi.org/10.1200/JCO.19.00416.
Su L, Shi YY, Liu ZY, et al. Acute myeloid leukemia with CEBPA mutations: Current progress and future directions. Front Oncol 2022; 12: 806137. https://doi.org/10.3389/ fonc.2022.806137.
Ohlsson E, Schuster MB, Hasemann M, et al. The mul- tifaceted functions of C/EBPα in normal and malignant haematopoiesis. Leukemia 2016; 30 (4): 767–75. https:// doi.org/10.1038/leu.2015.324.
Wakita S, Sakaguchi M, Oh I, et al. Prognostic impact of CEBPA bZIP domain mutation in acute myeloid leukemia. Blood Adv 2022; 6 (1): 238–47. https://doi.org/10.1182/ bloodadvances.2021004292.
Xiao W, Nardi V, Stein E, et al. A practical approach on the classifications of myeloid neoplasms and acute leukemia: WHO and ICC. J Hematol Oncol 2024; 17 (1): 56. https:// doi.org/10.1186/s13045-024-01571-4.
Taskesen E, Bullinger L, Corbacioglu A, et al. 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 2011; 117 (8): 2469–75. https://doi.org/10.1182/ blood-2010-09-307280.
Chen X, Abuduaini D, Zhang Y, et al. Characteristic im- munophenotype and gene co-mutational status orchestrate to optimize the prognosis of CEBPA mutant acute myeloid leukemia. Blood Cancer J 2023; 13 (1): 70. https://doi. org/10.1038/s41408-023-00838-2.
Fasan A, Haferlach C, Alpermann T, et al. The role of dif- ferent genetic subtypes of CEBPA mutated AML. Leuke- mia 2014; 28 (4): 794–803. https://doi.org/10.1038/leu. 2013.273.
Zhang F, Shen Z, Xie J, et al. CEBPA bZIP in-frame muta- tions in acute myeloid leukemia: Prognostic and therapeutic implications. Blood Cancer J 2024; 14 (1): 59. https://doi. org/10.1038/s41408-024-01042-6.
Ahn JS, Kim M, Ahn SY, et al. The co-occurrence of bZIP in-frame CEBPA-mutation with unfavorable genetic abnor- malities is associated with a poor prognosis in acute myeloid leukemia. Blood 2023; 142 (Suppl 1): 6035. https://doi. org/10.1182/blood-2023-180499.
Wang L, Chu X, Wang J, et al. Clinical characteristics and optimal therapy of acute myeloid leukemia with myelodys- plasia-related changes: A retrospective analysis of a cohort of Chinese patients. Turk J Haematol 2021; 38 (3): 188–94. https://doi.org/10.4274/tjh.galenos.2021.2021.0009.
Shallis RM, Wang R, Davidoff A, et al. Epidemiology of acute myeloid leukemia: Recent progress and endur- ing challenges. Blood Rev 2019; 36: 70–87. https://doi. org/10.1016/j.blre.2019.04.005.
Bowen D, Culligan D, Jowitt S, et al. Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol 2003; 120 (2): 187–200. https://doi.org/ 10.1046/j.1365-2141.2003.03907.x.
Koenig KL, Sahasrabudhe KD, Sigmund AM, et al. AML with myelodysplasia-related changes: Development, chal- lenges, and treatment advances. Genes (Basel) 2020; 11 (8): 845. https://doi.org/10.3390/genes11080845.
Gruber TA, Larson Gedman A, Zhang J, et al. An inv(16) (p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryo- blastic leukemia. Cancer Cell 2012; 22 (5): 683–97. https:// doi.org/10.1016/j.ccr.2012.10.007.
Thiollier C, Lopez CK, Gerby B, et al. Characterization of novel genomic alterations and therapeutic approaches using acute megakaryoblastic leukemia xenograft models. J Exp Med 2012; 209 (11): 2017–31. https://doi.org/10.1084/ jem.20121343.
Xie W, Hu S, Xu J, et al. Acute myeloid leukemia with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP in adults. Ann Hematol 2019; 98 (5): 1149–57. https://doi.org/10.1007/ s00277-019-03637-7.
Morgan R, Riske CB, Meloni A, et al. t(16;21)(p11.2;q22): A recurrent primary rearrangement in ANLL. Cancer Genet Cytogenet 1991; 53 (1): 83–90. https://doi.org/10.1016/ 0165-4608(91)90117-d.
Buchanan J, Tirado CA. A t(16;21)(p11;q22) in acute mye- loid leukemia (AML) resulting in fusion of the FUS/TLS and ERG genes: A review of the literature. J Assoc Genet Technol 2016; 42 (1): 24–33. PMID: 27183148.
Bousquets-Muñoz P, Molina O, Varela I, et al. Backtracking NOM1::ETV6 fusion to neonatal pathogenesis of t(7;12) (q36;p13) infant AML. Leukemia 2024; 38 (8): 1808–12. https://doi.org/10.1038/s41375-024-02293-9.
Lim G, Choi JR, Kim MJ, et al. Detection of t(3;5) and NPM1/MLF1 rearrangement in an elderly patient with acute myeloid leukemia: Clinical and laboratory study with review of the literature. Cancer Genet Cytogenet 2010; 199 (2): 101–9. https://doi.org/10.1016/j.cancergencyto.
02.009.
Tao S, Song L, Deng Y, et al. Acute myeloid leukemia with NUP98-RARG gene fusion similar to acute promyelocytic leukemia: Case report and literature review. Onco Targets Ther 2020; 13: 10559–66. https://doi.org/10.2147/OTT. S273172.
