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Review

Uncommon Cytogenetic Abnormalities Identifying High-Risk Acute Myeloid Leukemia in Children

, ORCID Icon, , , &
Pages 2747-2762 | Received 20 May 2020, Accepted 20 Jul 2020, Published online: 19 Aug 2020

References

  • Zwaan CM , KolbEA, ReinhardtDet al. Collaborative efforts driving progress in pediatric acute myeloid leukemia. J. Clin. Oncol.33(27), 2949–2962 (2015).
  • Rasche M , ZimmermannM, BorschelLet al. Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. Leukemia32(10), 2167–2177 (2018).
  • Pession A , MasettiR, RizzariCet al. Results of the AIEOP AML 2002/01 multicenter prospective trial for the treatment of children with acute myeloid leukemia. Blood122(2), 170–178 (2013).
  • Buldini B , Maurer-GranofszkyM, VarottoE, DworzakMN. Flow-cytometric monitoring of minimal residual disease in pediatric patients with acute myeloid leukemia: recent advances and future strategies. Front. Pediatr.11(7), 412 (2019).
  • Buldini B , RizzatiF, MasettiRet al. Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol. Br. J. Haematol.177(1), 116–126 (2017).
  • Pession A , LonettiA, BertuccioS, LocatelliF, MasettiR. Targeting hedgehog pathway in pediatric acute myeloid leukemia: challenges and opportunities. Expert Opin. Ther. Targets23(2), 87–91 (2019).
  • Bolouri H , FarrarJE, TricheTet al. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions. Nat. Med.24(1), 103–112 (2018).
  • de Rooij JD , MasettiR, denvan Heuvel-eibrink MMet al. Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: a retrospective intergroup study. Blood127(26), 3424–3431 (2016).
  • de Rooij JD , BranstetterC, MaJet al. Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. Nat. Genet.74(1), 27–34 (2017).
  • Masetti R , GuidiV, RonchiniL, BertuccioNS, LocatelliF, PessionA. The changing scenario of non-Down syndrome acute megakaryoblastic leukemia in children. Crit. Rev. Oncol. Hematol.138, 132–138 (2019).
  • Inaba H , ZhouY, AblaOet al. Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study. Blood126(13), 1575–1584 (2015).
  • Masetti R , PigazziM, TogniMet al. CBFA2T3-GLIS2 fusion transcript is a novel common feature in pediatric, cytogenetically normal AML, not restricted to FAB M7 subtype. Blood121(17), 3469–3472 (2013).
  • de Rooij JD , HollinkI, Arentsen-petersSet al. NUP98/JARID1A is a novel recurrent abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern. Leukemia27(12), 2280–2288 (2013).
  • Schwartz S , JijiR, KermanS, MeekinsJ, CohenMM. Translocation (6;9)(p23;q34) in acute nonlymphocytic leukemia. Cancer Genet. Cytogenet.18(4), 133–138 (1983).
  • Slovak M , GundackerH, BloomfieldCD, HeeremaNA. A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare ´poor prognosis´ myeloid malignancies. Leukemia20(7), 1295–1297 (2006).
  • Tarlock K , ToddA, MoraledaPPet al. Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is associated with poor outcome in childhood AML regardless of FLT3-ITD status: a report from the Children’s Oncology Group. Br. J. Haematol.166(2), 254–259 (2014).
  • Sandahl JD , CoenenEA, ForestierEet al. t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients. Haematologica99(5), 865–872 (2014).
  • Panagopoulos I , ÅmanP, FioretosT, HöglundM, JohanssonB, MitelmanF. Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22). Genes Chromosomes Cancer11(4), 256–262 (1994).
  • Gamou T , KitamuraE, HosodaFet al. The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family. Blood91(11), 4028–4037 (1998).
  • Noort S , ZimmermannM, ReinhardtDet al. Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM study group. Blood132(15), 1584–1593 (2018).
  • Tomizawa D , YoshidaM, KondoT, MiyamuraT, TagaT. Allogeneic hematopoietic stem cell transplantation for children and adolescents with high-risk cytogenetic AML: distinctly poor outcomes of FUS-ERG-positive cases. Bone Marrow Transplant.54(3), 393–401 (2019).
  • Ismael O , ShimadaA, ElmahdiS, ElshazleyM. RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22). Int. J. Hematol.99(2), 169–174 (2014).
  • Zerkalenkova E , PanfyorovaA, KazakovaAet al. Molecular characteristic of acute leukemias with t(16;21)/FUS-ERG. Ann. Hematol.97(6), 977–988 (2018).
  • Kong BX , IdaK, IchikawaHet al. Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16; 21)(p11; q22) and identification of a novel transcript. Blood90(3), 1192–1199 (1997).
  • Imashuku S , HibiS, SakoM, LinY, TsunematsuY. Hemophagocytosis by leukemic blasts in 7 acute myeloid leukemia cases with t(16;21)(p11;q22): common morphologic characteristics for this type of leukemia. Cancer88(8), 1970–1975 (2000).
  • Coenen EA , ZwaanCM, ReinhardtDet al. Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Muenster AML-study group. Blood122(15), 2704–2713 (2013).
  • Gomes Andrade F , PereiraE, MariaRet al. Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis. Brazilian J. Hematol. Hemotherapy8(4), 291–297 (2016).
  • Hollink IHIM , vanden Heuvel-Eibrink MM, Arentsen-PetersSTCJMet al. NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern. Blood118(13), 3645–3656 (2011).
  • Romana S , Radford-WeissI, BenAbdelali Ret al. NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique. Leukemia20(4), 696–706 (2006).
  • Cerveira N , CorreiaC, DoriaSet al. Frequency of NUP98-NSD1 fusion transcript in childhood acute myeloid leukaemia. Leukemia17(11), 2244–2247 (2003).
  • Hara Y , ShibaN, OhkiKet al. Prognostic impact of specific molecular profiles in pediatric acute megakaryoblastic leukemia in non-Down syndrome. Genes Chromosomes Cancer56(5), 394–404 (2017).
  • von Bergh ARM , van DrunenE, Van WeringERet al. High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a dismal outcome and ectopic expression of HLXB9. Genes Chromosomes Cancer45(8), 731–739 (2006).
  • Satake N , MasekiN, NishiyamaMet al. Chromosome abnormalities and MLL rearrangements in acute myeloid leukemia of infants. Leukemia13(7), 1013–1017 (1999).
  • Chi Y , LindgrenV, QuigleyS, GaitondeS. Acute myelogenous leukemia with t(6;9)(p23;q34) and marrow basophilia. Arch. Pathol. Lab. Med.132(11), 1835–1837 (2008).
  • Zwaan CM , MeshinchiS, RadichJPet al. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood102(7), 2387–2394 (2003).
  • Akiki S , DyerSA, GrimwadeDet al. NUP98-NSD1 fusion in association with FLT3-ITD mutation identifies a prognostically relevant subgroup of pediatric acute myeloid leukemia patients suitable for monitoring by real time quantitative PCR. Genes Chromosomes Cancer52(11), 1053–1064 (2013).
  • Pigazzi M , ManaraE, BresolinSet al. MicroRNA-34b promoter hypermethylation induces CREB overexpression and contributes to myeloid transformation. Haematologica98(4), 602–610 (2013).
  • Ostronoff F , OthusM, GerbingRBet al. NUP98/NSD1 and FLT3/ITD coexpression is more prevalent in younger AML patients and leads to induction failure: a COG and SWOG report. Blood124(15), 2400–2408 (2014).
  • Taketani T , TakiT, NakamuraTet al. High frequencies of simultaneous FLT3-ITD, WT1 and KIT mutations in hematological malignancies with NUP98-fusion genes. Leukemia24(11), 1975–1977 (2010).
  • Fasan A , HaferlachC, AlpermannT, KernW, HaferlachT, SchnittgerS. A rare but specific subset of adult AML patients can be defined by the cytogenetically cryptic NUP98-NSD1 fusion gene. Leukemia27(1), 245–248 (2013).
  • Thol F , KölkingB, HollinkIHIet al. Analysis of NUP98/NSD1 translocations in adult AML and MDS patients. Leukemia27(3), 750–754 (2013).
  • Masetti R , TogniM, AstolfiAet al. DHH-RHEBL1 fusion transcript: a novel recurrent feature in the new landscape of pediatric CBFA2T3-GLIS2-positive acute myeloid leukemia. Oncotarget4(10), 1712–1720 (2013).
  • Elgarten CW , AplencR. Pediatric acute myeloid leukemia: updates on biology, risk stratification, and therapy. Curr. Opin. Pediatr.32(1), 57–66 (2020).
  • Qin H , MalekS, CowellJK, RenM. Transformation of human CD34+ hematopoietic progenitor cells with DEK-NUP214 induces AML in an immunocompromised mouse model. Oncogene35(43), 5686–5691 (2016).
  • Sandén C , AgebergM, PeterssonJ, LennartssonA, GullbergU. Forced expression of the DEK-NUP214 fusion protein promotes proliferation dependent on upregulation of mTOR. BMC Cancer13, 440 (2013).
  • Harrison CJ , HillsRK, MoormanAVet al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council treatment trials AML 10 and 12. J. Clin. Oncol.28(16), 2674–2681 (2010).
  • Díaz-Beyá M , LabopinM, MaertensJet al. Allogeneic stem cell transplantation in AML with t(6;9)(p23;q34);DEK-NUP214 shows a favourable outcome when performed in first complete remission. Br. J. Haematol.189(5), 920–925 (2020).
  • Kayser S , HillsRK, LuskinMRet al. Allogeneic hematopoietic cell transplantation improves outcome of adults with t(6;9) acute myeloid leukemia: results from an international collaborative study. Haematologica105(1), 161–169 (2020).
  • Stone RM , MandrekarSJ, SanfordBLet al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N. Engl. J. Med.377(5), 454–464 (2017).
  • Jekarl WD , KimM, LimJet al. CD56 antigen expression and hemophagocytosis of leukemic cells in acute myeloid leukemia with t(16;21)(p11;q22). Int. J. Hematol.92(2), 306–313 (2010).
  • Marosi C , BettelheimP, GeisslerKet al. Acute monoblastic leukemia with erythrophagocytosis. Cancer Genet. Cytogenet.54(1), 61–66 (1991).
  • Bock J , MochmannLH, SchleeCet al. ERG transcriptional networks in primary acute leukemia cells implicate a role for ERG in deregulated kinase signaling. PLoS ONE8(1), e52872 (2013).
  • Martens JHA , MandoliA, SimmerFet al. ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia. Blood120(19), 4038–4048 (2012).
  • Sotoca AM , PrangeKHM, ReijndersBet al. The oncofusion protein FUS-ERG targets key hematopoietic regulators and modulates the all-trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia. Oncogene35(15), 1965–1976 (2016).
  • Masetti R , VendeminiF, ZamaD, BiagiC, GasperiniP, PessionA. All-trans retinoic acid in the treatment of pediatric acute promyelocytic leukemia. Expert Rev. Anticancer Ther.12(9), 1191–1204 (2012).
  • Yao S , JianlinC, YarongLet al. Donor-derived CD123-targeted CAR T cell serves as a RIC regimen for haploidentical transplantation in a patient with FUS-ERG+ AML. Front. Oncol.9, 1358 (2019).
  • Wu X , SulavikD, RoulstonD, LimM. Spontaneous remission of congenital acute myeloid leukemia with t(8;16)(p11;13). Pediatr. Blood Cancer56(11), 331–332 (2011).
  • Diab A , ZicklL, Abdel-wahabOet al. Acute myeloid leukemia with translocation t(8;16) presents with features which mimic acute promyelocytic leukemia and is associated with poor prognosis. Leuk. Res.37(1), 32–36 (2013).
  • Barrett R , MarfleetL, MorashBet al. FISH identifies a KAT6A/CREBBP fusion caused by a cryptic insertional t(8;16) in a case of spontaneously remitting congenital acute myeloid leukemia with a normal karyotype. Pediatr. Blood Cancer64(8) (2017).
  • Weintraub M , KaplinskyC, AmariglioNet al. Spontaneous regression of congenital leukaemia with an 8;16 translocation. Br. J. Haematol.111(2), 641–643 (2000).
  • Díaz-Beyá M , NavarroA, FerrerGet al. Acute myeloid leukemia with translocation (8;16)(p11;p13) and MYST3-CREBBP rearrangement harbors a distinctive microRNA signature targeting RET proto-oncogene. Leukemia27(3), 595–603 (2013).
  • Camos M , EsteveJ, JaresPet al. Gene expression profiling of acute myeloid leukemia with rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression. Cancer Res.66(14), 6947–6955 (2006).
  • Murati A , GervaisC, CarbucciaNet al. Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases. Leukemia23(1), 85–94 (2009).
  • Haferlach T , KohlmannA, KleinHet al. AML with translocation t (8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features. Leukemia23(5), 934–943 (2009).
  • Baell JB , LeaverDJ, HermansSJet al. Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth. Nature560(7717), 253–257 (2018).
  • Jaju RJ , FidlerC, HaasOAet al. A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. Blood98(4), 1264–1268 (2001).
  • Struski S , LagardeS, BoriesPet al. NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis. Leukemia31(3), 565–572 (2017).
  • Noort S , WanderP, AlonzoTAet al. The clinical and biological characteristics of NUP98-KDM5A in pediatric acute myeloid leukemia. Haematologica doi:10.3324/haematol.2019.236745 (2020) (Epub ahead of print).
  • Shiba N , IchikawaH, TakiTet al. NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia. Genes Chromosomes Cancer52(7), 683–693 (2013).
  • Xu H , ValerioDG, EisoldMEet al. NUP98 fusion proteins interact with the NSL and MLL1 complexes to drive leukemogenesis. Cancer Cell30(6), 863–878 (2016).
  • Bisio V , ZampiniM, TregnagoCet al. NUP98-fusion transcripts characterize different biological entities within acute myeloid leukemia: a report from the AIEOP-AML group. Leukemia31(4), 974–977 (2017).
  • Lavallé V , LemieuxS, BoucherGet al. Identification of MYC mutations in acute myeloid leukemias with NUP98-NSD1 translocations. Leukemia30(7), 1621–1624 (2016).
  • Cardin S , BilodeauM, RoussyMet al. Human models of NUP98-KDM5A megakaryocytic leukemia in mice contribute to uncovering new biomarkers and therapeutic vulnerabilities. Blood Adv3(21), 3307–3321 (2019).
  • Gruber TA , LarsonGedman A, ZhangJet al. An inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia. Cancer Cell29(10), 1883–1889 (2012).
  • Thiollier C , LopezCK, GerbyBet al. Characterization of novel genomic alterations and therapeutic approaches using acute megakaryoblastic leukemia xenograft models. J. Exp. Med.209(11), 2017–2031 (2012).
  • Masetti R , BertuccioSN, AstolfiAet al. Hh/Gli antagonist in acute myeloid leukemia with CBFA2T3-GLIS2 fusion gene. J. Hematol. Oncol.10(1), 26 (2017).
  • Masetti R , RondelliR, FagioliFet al. Infants with acute myeloid leukemia treated according to the Associazione Italiana di Ematologia e Oncologia Pediatrica 2002/01 protocol have an outcome comparable to that of older children. Haematologica99(8), 127–129 (2014).
  • Lopez CK , NogueraE, StavropoulouVet al. Ontogenic changes in hematopoietic hierarchy determine pediatric specificity and disease phenotype in fusion oncogene–driven myeloid leukemia. Cancer Discov.9(12), 1736–1753 (2019).
  • Creutzig U , DworzakMN, ZimmermannMet al. Characteristics and outcome in patients with central nervous system involvement treated in European pediatric acute myeloid leukemia study groups. Pediatr. Blood Cancer64(12) (2017).
  • Masetti R , BertuccioSN, PessionA, LocatelliF. CBFA2T3-GLIS2-positive acute myeloid leukaemia. A peculiar paediatric entity. Br. J. Haematol.184(3), 337–347 (2019).
  • Thirant C , IgnacimouttouC, LopezCKet al. ETO2-GLIS2 hijacks transcriptional complexes to drive cellular identity and self-renewal in pediatric acute megakaryoblastic leukemia. Cancer Cell31(3), 452–465 (2017).
  • Thirant C , LopezC, MalingeS, MercherT. Molecular pathways driven by ETO2-GLIS2 in aggressive pediatric leukemia. Mol. Cell. Oncol.4(6), e1345351 (2017).
  • Eidenschink Brodersen L , AlonzoT, MenssenAet al. A recurrent immunophenotype at diagnosis independently identifies high-risk pediatric acute myeloid leukemia: a report from Children’s Oncology Group. 30(10), 2077–2080 (2016).
  • Wen Q , GoldensonB, SilverSJet al. Integrative screening approach identifies regulators of polyploidization and targets for acute megakaryocytic leukemia. Cell150(3), 575–589 (2012).
  • Wichmann C , ChenL, HeinrichMet al. Targeting the oligomerization domain of ETO interferes with RUNX1/ETO oncogenic activity in t(8;21)-positive leukemic cells. Cancer Res.67(5), 2280–2289 (2007).
  • Pan D , LiY, LiZ, WangY, WangP, LiangY. Gli inhibitor GANT61 causes apoptosis in myeloid leukemia cells and acts in synergy with rapamycin. Leuk. Res.36(6), 742–748 (2012).
  • Agyeman A , JhaBK, MazumdarT, HoughtonJA. Mode and specificity of binding of the small molecule GANT61 to GLI determines inhibition of GLI-DNA binding. Oncotarget5(12), 4492–4503 (2014).
  • Vasanth S , ZeRuthG, KangHS, JettenAM. Identification of nuclear localization, DNA binding, and transactivating mechanisms of krüppel-like zinc finger protein gli-similar 2 (GLIS2). J. Biol. Chem.286(6), 4749–4759 (2011).
  • Naiel A , VetterM, PlekhanovaOet al. A novel three-colour fluorescence in situ hybridization approach for the detection of t(7;12)(q36;p13) in acute myeloid leukaemia reveals new cryptic three way translocation t(7;12;16). Cancers (Basel)5(1), 281–295 (2013).
  • Park J , KimM, LimJet al. Three-way complex translocations in infant acute myeloid leukemia with t(7;12)(q36;p13): the incidence and correlation of a HLXB9 overexpression. Cancer Genet. Cytogenet.191(2), 102–105 (2009).
  • Tosi S , KamelYM, OwokaT, FedericoC, TruongTH, SacconeS. Paediatric acute myeloid leukaemia with the t(7;12)(q36;p13) rearrangement: a review of the biological and clinical management aspects. Biomark. Res.3, 21 (2015).
  • Tosi S , HughesJ, SchererSWet al. Heterogeneity of the 7q36 breakpoints in the t (7;12) involving ETV6 in infant leukemia. Genes Chromosomes Cancer38(2), 191–200 (2003).
  • Espersen ADL , HaS, HasleH, AbrahamssonJ, Noren-nystrUJG. Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is associated with infancy and trisomy 19: data from Nordic Society for Pediatric Hematology and Oncology (NOPHO-AML) and review of the literature. Genes Chromosomes Cancer57(7), 359–365 (2018).
  • Webb DKH , HarrisonG, StevensRF, GibsonBG, HannIM. Relationships between age at diagnosis, clinical features, and outcome of therapy in children treated in the Medical Research Council AML 10 and 12 trials for acute myeloid leukemia. Blood98(6), 1714–1721 (2001).
  • Harrison CJ , HillsRK, MoormanAVet al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council treatment trials AML 10 and 12. J. Clin. Oncol.28(16), 2674–2681 (2010).
  • Chessells JM , HarrisonCJ, KempskiHet al. Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukaemia working party. Leukemia16(5), 776–784 (2002).
  • Beverloo HB , PanagopoulosI, IsakssonMet al. Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13). Cancer Res.61(14), 5374–5377 (2001).
  • Zhou F , ChenB. Acute myeloid leukemia carrying ETV6 mutations: biologic and clinical features. Hematology23(9), 608–612 (2018).
  • Ballabio E , CantarellaC, FedericoCet al. Ectopic expression of the HLXB9 gene is associated with an altered nuclear position in t(7;12) leukaemias. Leukemia23(6), 1179–1182 (2009).
  • Tosi S , HarbottJ, Teigler-schlegelAet al. t(7;12)(q36;p13), a new recurrent translocation involving ETV6 in infant leukemia. Genes Chromosomes Cancer29(4), 325–332 (2000).
  • Hirsch B , AlonzoTA, GerbingRBet al. Abnormalities of 12p are associated with high-risk acute myeloid leukemia: a Children’s Oncology Group report. Blood122(21), 612 (2013).
  • Simmons HM , OsethL, NguyenP, LearyMO, ConklinKF, HirschB. Cytogenetic and molecular heterogeneity of 7q36/12p13 rearrangements in childhood AML. Leukemia16(12), 2408–2416 (2002).
  • Ward E , DesantisC, RobbinsA, KohlerB, JemalA. Childhood and adolescent cancer statistics, 2014. CA Cancer J. Clin.64(2), 83–103 (2014).
  • Wildenhain S , RuckertC, RöttgersSet al. Expression of cell–cell interacting genes distinguishes HLXB9/TEL from MLL-positive childhood acute myeloid leukemia. Leukemia24(9), 1657–1660 (2010).
  • Taketani T , TakiT, SakoM, IshiiT. MNX1-ETV6 fusion gene in an acute megakaryoblastic leukemia and expression of the MNX1 gene in leukemia and normal B cell lines. Cancer Genet. Cytogenet.186(2), 115–119 (2008).
  • Nagel S , EhrentrautS, MeyerC, KaufmannM, DrexlerHG, MacLeodRAF. Oncogenic deregulation of NKL homeobox gene MSX1 in mantle cell lymphoma. Leuk. Lymphoma.55(8), 1893–1903 (2014).
  • Neufing PJ , KalionisB, HorsfallDJet al. Expression and localization of homeodomain proteins DLX4/HB9 in normal and malignant human breast tissues. Anticancer Res.23(2B), 1479–1488 (2003).
  • Almstrup K , LeffersH, LotheRAet al. Improved gene expression signature of testicular carcinoma in situ. Int. J. Androl.30(4), 292–302 (2007).
  • Wilkens L , JaggiR, HammerC, InderbitzinD, GigerO, von NeuhoffN. The homeobox gene HLXB9 is upregulated in a morphological subset of poorly differentiated hepatocellular carcinoma. Virchows Arch.458(6), 697–708 (2011).
  • El-Khazragy N , GhozyS, MatboulySet al. Interaction between 12p chromosomal abnormalities and Lnc–HOTAIR mediated pathway in acute myeloid leukemia. J. Cell. Biochem.120(9), 15288–15296 (2019).
  • de Rooij J , BeulingE, FornerodM, ObulkasimA, BaruchelA, TrkaJ. ETV6 aberrations are a recurrent event in pediatric acute myeloid leukemia with poor clinical outcome. Blood124(21), 1012 (2014).
  • Hernandez JM , GonzalezMB, GarciaJLet al. Two cases of myeloid disorders and a t(8;12)(q12;p13). Haematologica85(1), 31–34 (2000).
  • Slater RM , DrunenE, KroesWGet al. t(7;12)(q36;p13) and t(7;12)(q32;p13) – translocations involving ETV6 in children 18 months of age or younger with myeloid disorders. Leukemia15(6), 915–920 (2001).
  • Bertuccio SN , BoudiaF, CambotMet al. The pediatric acute leukemia fusion oncogene ETO2-GLIS2 increases self-renewal and alters differentiation in a human induced pluripotent stem cells–derived model. HemaSphere4(1), e319 (2020).

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