Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.

Biological Hematology AP HP A Trousseau Pierre et Marie Curie University Paris France

Bristol Genetics Laboratory North Bristol NHS Trust Bristol United Kingdom

Centro di Riferimento Regionale di Ematologia ed Oncologia Pediatrica Azienda Policlinico G Rodolico Catania Italy

Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin Department of Pediatric Oncology Hematology Berlin Germany

Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin Dept of Hematology Oncology and Tumor Immunology Berlin Germany

CLIP Department of Paediatric Haematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Cytogenetics Department Bone Marrow Transplantation Unit National Cancer Institute Rio de Janeiro Brazil

DCAL Institute of Pharm Biology Goethe University Frankfurt Main Germany

Department of Clinical Chemistry and Laboratory Division University of Turku and Turku University Hospital Turku Finland

Department of Clinical Immunology Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Hematology CHU Lille France

Department of Immunology Erasmus MC University Medical Center Rotterdam Rotterdam Netherlands

Department of Laboratory Medicine Wonju Severance Christian Hospital Yonsei University Wonju College of Medicine Wonju Korea

Department of Pediatric Hematology and Oncology Medical University of Silesia Zabrze Poland

Department of Pediatrics MHH Hanover Germany

Department of Pediatrics University Hospital Schleswig Holstein Kiel Germany

Division of Oncology and Children's Research Centre University Children's Hospital Zurich Zurich Switzerland

Division of Pediatric Hematology Oncology 1st Department of Pediatrics National and Kapodistrian University of Athens Aghia Sophia Children's Hospital Athens Greece

Genetics and Personalized Medicine Clinic Tartu University Hospital Tartu Estonia

Genetics Department AP HP Hopital Robert Debré Paris France

Hematology Laboratory Saint Louis Hospital Assistance Publique Hôpitaux de Paris Paris France

Hematology Laboratory Sheba Medical Center Tel Hashomer Israel

Institut Universitaire du Cancer de Toulouse Toulouse Cedex 9 France

Institute of Human Genetics Medical School Hannover Hannover Germany

Instituto Nacional de Câncer Rio de Janeiro RJ Brazil

Instituto Português de Oncologia Departament of Hematology Lisbon Portugal

Josep Carreras Leukemia Research Institute Barcelona Spanish Network for Advanced Therapies ; University of Barcelona Barcelona Spain

Josep Carreras Leukemia Research Institute Barcelona Spanish Network for Advanced Therapies Barcelona Spain

Labdia Labordiagnostik Vienna Austria

Laboratoire d'Hématologie Biologique CHU Bordeaux Bordeaux France

Laboratory for Specialized Hematological Diagnostics Medical Department 2 University Hospital Schleswig Holstein Kiel Germany

Laboratory of Clinical Genetics Fimlab Laboratories Tampere Finland

Molecular Diagnostics Children's Cancer Institute Lowy Cancer Research Centre UNSW Sydney NSW Australia

Molecular Oncology Laboratory Schneider Children's Medical Center of Israel Petah Tikva Israel

Northern Institute for Cancer Research Newcastle University and the Great North Children's West Midlands Regional Genetics Laboratory Birmingham Women's and Children's NHS Foundation Trust Mindelsohn Way Birmingham United Kingdom

Pediatric Hematology and Oncology and CoALL Study Center University Medical Center Hamburg Eppendorf Hamburg Germany

Pediatric Hematology Oncology Schneider Children's Medical Center Petah Tikva and Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

Princess Máxima Center for Pediatric Oncology Utrecht Netherlands

Regional Children's Hospital Ekaterinburg Russian Federation; Research Institute of Medical Cell Technologies Ekaterinburg Russian Federation

St Anna Children's Cancer Research Institute Vienna Austria

St Anna Children's Hospital Medical University of Vienna Vienna Austria

Tettamanti Research Center Pediatrics University of Milano Bicocca Fondazione Tettamanti Monza Italy

Université Paris Cité INSERM CNRS U944 UMR7212 Institut de recherche Saint Louis Paris France

Université Paris Cité Inserm U1131 Institut de recherche Saint Louis Paris France

Wolfson Childhood Cancer Research Centre Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne United Kingdom

See more in PubMed

Pui CH, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W, et al. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. The Lancet. 2002;359:1909–15. doi: 10.1016/S0140-6736(02)08782-2. PubMed DOI

Pui CH, Chessells JM, Camitta B, Baruchel A, Biondi A, Boyett JM, et al. Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements. Leukemia. 2003;17:700–6. doi: 10.1038/sj.leu.2402883. PubMed DOI

Balgobind BV, Raimondi SC, Harbott J, Zimmermann M, Alonzo TA, Auvrignon A, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood. 2009;114:2489–96. doi: 10.1182/blood-2009-04-215152. PubMed DOI PMC

Szczepański T, Harrison CJ, van Dongen JJ. Genetic aberrations in paediatric acute leukaemias and implications for management of patients. Lancet Oncol. 2010;11:880–9. doi: 10.1016/S1470-2045(09)70369-9. PubMed DOI

Burmeister T, Marschalek R, Schneider B, Meyer C, Gökbuget N, Schwartz S, et al. Monitoring minimal residual disease by quantification of genomic chromosomal breakpoint sequences in acute leukemias with MLL aberrations. Leukemia. 2006;20:451–7. doi: 10.1038/sj.leu.2404082. PubMed DOI

van der Velden VH, Corral L, Valsecchi MG, Jansen MW, De Lorenzo P, Cazzaniga G, et al. Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol. Leukemia. 2009;23:1073–9. doi: 10.1038/leu.2009.17. PubMed DOI

Yeoh AE, Ariffin H, Chai EL, Kwok CS, Chan YH, Ponnudurai K, et al. Minimal residual disease-guided treatment deintensification for children with acute lymphoblastic leukemia: results from the Malaysia-Singapore acute lymphoblastic leukemia 2003 study. J Clin Oncol. 2012;30:2384–92. doi: 10.1200/JCO.2011.40.5936. PubMed DOI

Johansson B, Moorman AV, Secker-Walker LM. Derivative chromosomes of 11q23-translocations in hematologic malignancies. European 11q23 Workshop participants. Leukemia. 1998;12:828–33. doi: 10.1038/sj.leu.2401019. PubMed DOI

Heerema NA, Sather HN, Ge J, Arthur DC, Hilden JM, Trigg ME, et al. Cytogenetic studies of infant acute lymphoblastic leukemia: poor prognosis of infants with t(4;11) - a report of the Children’s Cancer Group. Leukemia. 1999;13:679–86. doi: 10.1038/sj.leu.2401413. PubMed DOI

Van der Burg M, Beverloo HB, Langerak AW, Wijsman J, van Drunen E, Slater R, et al. Rapid and sensitive detection of all types of MLL gene translocations with a single FISH probe set. Leukemia. 1999;13:2107–13. doi: 10.1038/sj.leu.2401595. PubMed DOI

van der Burg M, Poulsen TS, Hunger SP, Beverloo HB, Smit EM, Vang-Nielsen K, et al. Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia. Leukemia. 2004;18:895–908. doi: 10.1038/sj.leu.2403340. PubMed DOI

Harrison CJ, Moorman AV, Barber KE, Broadfield ZJ, Cheung KL, Harris RL, et al. Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia: a UK Cancer Cytogenetics Group Study. Br J Haematol. 2005;129:520–30. doi: 10.1111/j.1365-2141.2005.05497.x. PubMed DOI

Burmeister T, Meyer C, Gröger D, Hofmann J, Marschalek R. Evidence-based RT-PCR methods for the detection of the 8 most common MLL aberrations in acute leukemias. Leuk Res. 2015;39:242–7. doi: 10.1016/j.leukres.2014.11.017. PubMed DOI

Meyer C, Schneider B, Reichel M, Angermueller S, Strehl S, Schnittger S, et al. Diagnostic tool for the identification of MLL rearrangements including unknown partner genes. Proc Natl Acad Sci USA. 2005;102:449–54. doi: 10.1073/pnas.0406994102. PubMed DOI PMC

Afrin S, Zhang CRC, Meyer C, Stinson CL, Pham T, Bruxner TJC, et al. Targeted Next-Generation Sequencing for Detecting MLL Gene Fusions in Leukemia. Mol Cancer Res. 2018;16:279–85. doi: 10.1158/1541-7786.MCR-17-0569. PubMed DOI

Meyer C, Lopes BA, Caye-Eude A, Cavé H, Arfeuille C, Cuccuini W, et al. Human MLL/KMT2A gene exhibits a second breakpoint cluster region for recurrent MLL-USP2 fusions. Leukemia. 2019;33:2306–40. doi: 10.1038/s41375-019-0451-7. PubMed DOI PMC

Meyer C, Schneider B, Jakob S, Strehl S, Schnittger S, Schoch C, et al. The MLL recombinome of acute leukemias. Leukemia. 2006;20:777–84. doi: 10.1038/sj.leu.2404150. PubMed DOI

Meyer C, Kowarz E, Hofmann J, Renneville A, Zuna J, Trka J, et al. New insights into the MLL recombinome of acute leukemias. Leukemia. 2009;23:1490–9. doi: 10.1038/leu.2009.33. PubMed DOI

Meyer C, Hofmann J, Burmeister T, Gröger D, Park TS, Emerenciano M, et al. The MLL recombinome of acute leukemia in 2013. Leukemia. 2013;27:2165–76. doi: 10.1038/leu.2013.135. PubMed DOI PMC

Meyer C, Burmeister T, Gröger D, Tsaur G, Fechina L, Renneville A, et al. The MLL recombinome of acute leukemias in 2017. Leukemia. 2018;32:273–84. doi: 10.1038/leu.2017.213. PubMed DOI PMC

Daser A, Rabbitts TH. The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis. Semin Cancer Biol. 2005;15:175–88. doi: 10.1016/j.semcancer.2005.01.007. PubMed DOI

Krivtsov AV, Armstrong SA. MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer. 2007;7:823–33. doi: 10.1038/nrc2253. PubMed DOI

Emerenciano M, Meyer C, Mansur MB, Marschalek R, Pombo-de-Oliveira MS, The Brazilian Collaborative Study Group of Infant Acute Leukaemia. The distribution of MLL breakpoints correlates with outcome in infant acute leukaemia. Br J Haematol. 2013;161:224–36. doi: 10.1111/bjh.12250. PubMed DOI

Strissel PL, Strick R, Rowley JD, Zeleznik-Le NJ. An in vivo topoisomerase II cleavage site and a DNase I hypersensitive site colocalize near exon 9 in the MLL breakpoint cluster region. Blood. 1998;92:3793–803. doi: 10.1182/blood.V92.10.3793. PubMed DOI

Stanulla M, Wang J, Chervinsk DS, Thandla S, Aplan PD. DNA cleavage within the MLL breakpoint cluster region is a specific event which occurs as part of higher-order chromatin fragmentation during the initial stages of apoptosis. Mol Cell Biol. 1997;17:4070–9. doi: 10.1128/MCB.17.7.4070. PubMed DOI PMC

Scharf S, Zech J, Bursen A, Schraets D, Oliver PL, Kliem S, et al. Transcription linked to recombination: a gene-internal promoter coincides with the recombination hot spot II of the human MLL gene. Oncogene. 2007;26:1361–71. doi: 10.1038/sj.onc.1209948. PubMed DOI

Felix CA. Leukemias related to treatment with DNA topoisomerase II inhibitors. Med Pediatr Oncol. 2001;36:525–35. doi: 10.1002/mpo.1125. PubMed DOI

Rössler T, Marschalek R. An alternative splice process renders the MLL protein either into a transcriptional activator or repressor. Pharmazie. 2013;68:601–7. PubMed

Marschalek R. The reciprocal world of MLL fusions: A personal view. Biochim Biophys Acta Gene Regul Mech. 2020;1863:194547. doi: 10.1016/j.bbagrm.2020.194547. PubMed DOI

O’Byrne S, Elliott N, Rice S, Buck G, Fordham N, Garnett C, et al. Discovery of a CD10-negative B-progenitor in human fetal life identifies unique ontogeny-related developmental programs. Blood. 2019;134:1059–71. doi: 10.1182/blood.2019001289. PubMed DOI

Rice S, Jackson T, Crump NT, Fordham N, Elliott N, O’Byrne S, et al. A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program. Nat Commun. 2021;12:6905. doi: 10.1038/s41467-021-27270-z. PubMed DOI PMC

Kundu A, Kowarz E, Marschalek R. The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(6;11) Oncogene. 2021;40:5902–12. doi: 10.1038/s41388-021-01983-3. PubMed DOI PMC

Meyer C, Burmeister T, Strehl S, Schneider B, Hubert D, Zach O, et al. Spliced MLL fusions: a novel mechanism to generate functional chimeric MLL-MLLT1 transcripts in t(11;19)(q23;p13.3) leukemia. Leukemia. 2007;21:588–90. doi: 10.1038/sj.leu.2404542. PubMed DOI

Meyer C, Kowarz E, Yip SF, Wan TS, Chan TK, Dingermann T, et al. A complex MLL rearrangement identified five years after initial MDS diagnosis is causing out-of-frame fusions whithout progression to acute leukemia. Cancer Genetics. 2011;204:557–62. doi: 10.1016/j.cancergen.2011.10.001. PubMed DOI

Mori T, Nishimura N, Hasegawa D, Kawasaki K, Kosaka Y, Uchide K, et al. Persistent detection of a novel MLL-SACM1L rearrangement in the absence of leukemia. Leuk Res. 2010;34:1398–401. doi: 10.1016/j.leukres.2010.05.001. PubMed DOI

Ranta-Aho J, Olive M, Vandroux M, Roticiani G, Dominguez C, Johari M, et al. Mutation update for the ACTN2 gene. Hum Mutat. 2022;43:1745–56. doi: 10.1002/humu.24470. PubMed DOI PMC

Qiu Z, He L, Yu F, Lv H, Zhou Y. LncRNA FAM13A-AS1 Regulates Proliferation and Apoptosis of Cervical Cancer Cells by Targeting miRNA-205-3p/DDI2 Axis. J Oncol. 2022;2022:8411919. doi: 10.1155/2022/8411919. PubMed DOI PMC

Shen J, Shu M, Xie S, Yan J, Pan K, Chen S, et al. A Six-Gene Prognostic Risk Prediction Model In Hepatitis B Virus-Associated Hepatocellular Carcinoma. Clin Invest Med. 2021;44:E32–44. doi: 10.25011/cim.v44i3.37124. PubMed DOI

Durślewicz J, Klimaszewska-Wiśniewska A, Jóźwicki J, Antosik P, Kozerawski K, Grzanka D, et al. Prognostic significance of MATR3 in stage I and II non-small cell lung cancer patients. J Cancer Res Clin Oncol. 2022;148:3313–22. doi: 10.1007/s00432-022-04097-9. PubMed DOI PMC

Yang J, Lee SJ, Kwon Y, Ma L, Kim J. Tumor suppressive function of Matrin 3 in the basal-like breast cancer. Biol Res. 2020;53:42. doi: 10.1186/s40659-020-00310-6. PubMed DOI PMC

Cha HJ, Uyan Ö, Kai Y, Liu T, Zhu Q, Tothova Z, et al. Inner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture. Nat Commun. 2021;12:6241. doi: 10.1038/s41467-021-26574-4. PubMed DOI PMC

Tanigawa K, Maekawa M, Kiyoi T, Nakayama J, Kitazawa R, Kitazawa S, et al. SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9. J Cell Physiol. 2019;234:17280–94. doi: 10.1002/jcp.28346. PubMed DOI PMC

Mygind KJ, Störiko T, Freiberg ML, Samsøe-Petersen J, Schwarz J, Andersen OM, et al. Sorting nexin 9 (SNX9) regulates levels of the transmembrane ADAM9 at the cell surface. J Biol Chem. 2018;293:8077–88. doi: 10.1074/jbc.RA117.001077. PubMed DOI PMC

Bendris N, Schmid SL. Endocytosis, Metastasis and Beyond: Multiple Facets of SNX9. Trends Cell Biol. 2017;27:189–200. doi: 10.1016/j.tcb.2016.11.001. PubMed DOI PMC

Bendris N, Williams KC, Reis CR, Welf ES, Chen PH, Lemmers B, et al. SNX9 promotes metastasis by enhancing cancer cell invasion via differential regulation of RhoGTPases. Mol Biol Cell. 2016;27:1409–19. doi: 10.1091/mbc.E16-02-0101. PubMed DOI PMC

Sardou-Cezar I, Lopes BA, Andrade FG, Fonseca TCC, Fernandez TS, Larghero P, et al. Therapy-related acute myeloid leukemia with KMT2A-SNX9 gene fusion associated with a hyperdiploid karyotype after hemophagocytic lymphohistiocytosis. Cancer Genet. 2021;256-257:86–90. doi: 10.1016/j.cancergen.2021.05.001. PubMed DOI

Pathria G, Garg B, Wagner C, Garg K, Gschaider M, Jalili A, et al. RanBP3 Regulates Melanoma Cell Proliferation via Selective Control of Nuclear Export. J Invest Dermatol. 2016;136:264–74. doi: 10.1038/JID.2015.401. PubMed DOI

Zheng CC, Liao L, Liu YP, Yang YM, He Y, Zhang GG, et al. Blockade of Nuclear β-Catenin Signaling via Direct Targeting of RanBP3 with NU2058 Induces Cell Senescence to Suppress Colorectal Tumorigenesis. Adv Sci (Weinh) 2022;9:e2202528. doi: 10.1002/advs.202202528. PubMed DOI PMC

Bouchard A, Witalis M, Chang J, Panneton V, Li J, Bouklouch Y, et al. Hippo Signal Transduction Mechanisms in T Cell Immunity. Immune Netw. 2020;20:e36. doi: 10.4110/in.2020.20.e36. PubMed DOI PMC

Lin CH, Hsu TI, Chiou PY, Hsiao M, Wang WC, Chen YC, et al. Downregulation of STK4 promotes colon cancer invasion/migration through blocking β-catenin degradation. Mol Oncol. 2020;14:2574–88. doi: 10.1002/1878-0261.12771. PubMed DOI PMC

Bärlund M, Monni O, Weaver JD, Kauraniemi P, Sauter G, Heiskanen M, et al. Cloning of BCAS3 (17q23) and BCAS4 (20q13) genes that undergo amplification, overexpression, and fusion in breast cancer. Genes Chromosomes Cancer. 2002;35:311–7. doi: 10.1002/gcc.10121. PubMed DOI

Wang Z, Wang H, Wang Z, He S, Jiang Z, Yan C, et al. Associated analysis of PER1/TUBB2B with endometrial cancer development caused by circadian rhythm disorders. Med Oncol. 2020;37:90. doi: 10.1007/s12032-020-01415-4. PubMed DOI

Russo A, O’Bryan JP. Intersectin 1 is required for neuroblastoma tumorigenesis. Oncogene. 2012;31:4828–34. doi: 10.1038/onc.2011.643. PubMed DOI PMC

Gu F, Zhang H, Qin F, Liu X, Li W, Fu L, et al. Intersectin1-S, a multidomain adapter protein, is essential for malignant glioma proliferation. Glia. 2015;63:1595–605. doi: 10.1002/glia.22830. PubMed DOI

Lan C, Zhang H, Wang K, Liu X, Zhao Y, Guo Z, et al. The alternative splicing of intersectin 1 regulated by PTBP1 promotes human glioma progression. Cell Death Dis. 2022;13:835. doi: 10.1038/s41419-022-05238-1. PubMed DOI PMC

Di Stefano B, Luo EC, Haggerty C, Aigner S, Charlton J, Brumbaugh J, et al. The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis. Cell Stem Cell. 2019;25:622–38. doi: 10.1016/j.stem.2019.08.018. PubMed DOI PMC

Taniguchi K, Iwatsuki A, Sugito N, Shinohara H, Kuranaga Y, Oshikawa Y, et al. Oncogene RNA helicase DDX6 promotes the process of c-Myc expression in gastric cancer cells. Mol Carcinog. 2018;57:579–89. doi: 10.1002/mc.22781. PubMed DOI

Mück F, Bracharz S, Marschalek R. DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex. Am J Blood Res. 2016;6:28–45. PubMed PMC

Zhang T, Chen Y, Lin W, Zheng J, Liu Y, Zou J, et al. Prognostic and Immune-Infiltrate Significance of miR-222-3p and Its Target Genes in Thyroid Cancer. Front Genet. 2021;12:710412. doi: 10.3389/fgene.2021.710412. PubMed DOI PMC

Dobre M, Salvi A, Pelisenco IA, Vasilescu F, De Petro G, Herlea V, et al. Crosstalk Between DNA Methylation and Gene Mutations in Colorectal Cancer. Front Oncol. 2021;11:697409. doi: 10.3389/fonc.2021.697409. PubMed DOI PMC

Shao Y, Kong J, Xu H, Wu X, Cao Y, Li W, et al. OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis. Front Cell Dev Biol. 2021;9:570898. doi: 10.3389/fcell.2021.570898. PubMed DOI PMC

Hareedy AA, Rohim EZA, Al Sheikh SAM, Al Shereef ZAEA. Immunohistochemical Expression of PD-L1 and IDH1 with Detection of MGMT Promoter Methylation in Astrocytoma. Asian Pac J Cancer Prev. 2022;23:4333–8. doi: 10.31557/APJCP.2022.23.12.4333. PubMed DOI PMC

Zhong S, Ren JX, Yu ZP, Peng YD, Yu CW, Deng D, et al. Predicting glioblastoma molecular subtypes and prognosis with a multimodal model integrating convolutional neural network, radiomics, and semantics. J Neurosurg. 2022;2:1–10. doi: 10.3171/2022.10.JNS22801. PubMed DOI

Furini HH, Fukushima KSSQ, de Nóbrega M, de Souza MF, Rodrigues MRS, de Mattos BB, et al. An MGMT Allelic Variant Can Affect Biochemical Relapse in Prostate Cancer Patients. Anticancer Res. 2023;43:369–79. doi: 10.21873/anticanres.16172. PubMed DOI

Wächter K, Kowarz E, Marschalek R. Functional characterisation of different MLL fusion proteins by using inducible Sleeping Beauty vectors. Cancer Lett. 2014;352:196–202. doi: 10.1016/j.canlet.2014.06.016. PubMed DOI

Wilhelm A, Marschalek R. The role of reciprocal fusions in MLL-r acute leukemia: studying the chromosomal translocation t(4;11) Oncogene. 2021;40:6093–102. doi: 10.1038/s41388-021-02001-2. PubMed DOI PMC

Yang L, Ding L, Liang J, Chen J, Tang Y, Xue H, et al. Relatively favorable prognosis for MLL-rearranged childhood acute leukemia with reciprocal translocations. Pediatr Blood Cancer. 2018;65:e27266. doi: 10.1002/pbc.27266. PubMed DOI

Agraz-Doblas A, Bueno C, Bashford-Rogers R, Roy A, Schneider P, Bardini M, et al. Unraveling the cellular origin and clinical prognostic markers of infant B-cell acute lymphoblastic leukemia using genome-wide analysis. Haematologica. 2019;104:1176–88. doi: 10.3324/haematol.2018.206375. PubMed DOI PMC

Fair K, Anderson M, Bulanova E, Mi H, Tropschug M, Diaz MO. Protein interactions of the MLL PHD fingers modulate MLL target gene regulation in human cells. Mol Cell Biol. 2001;21:3589–97. doi: 10.1128/MCB.21.10.3589-3597.2001. PubMed DOI PMC

Xia ZB, Anderson M, Diaz MO, Zeleznik-Le NJ. MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. Proc Natl Acad Sci USA. 2003;100:8342–7. doi: 10.1073/pnas.1436338100. PubMed DOI PMC

Chang PY, Hom RA, Musselman CA, Zhu L, Kuo A, Gozani O, et al. Binding of the MLL PHD3 finger to histone H3K4me3 is required for MLL-dependent gene transcription. J Mol Biol. 2010;400:137–144. doi: 10.1016/j.jmb.2010.05.005. PubMed DOI PMC

Wang Z, Song J, Milne TA, Wang GG, Li H, Allis CD, et al. Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression. Cell. 2010;141:1183–94. doi: 10.1016/j.cell.2010.05.016. PubMed DOI PMC

Wang J, Muntean AG, Hess JL. ECSASB2 mediates MLL degradation during hematopoietic differentiation. Blood. 2012;119:1151–61. doi: 10.1182/blood-2011-06-362079. PubMed DOI PMC

Wang J, Muntean AG, Wu L, Hess JL. A subset of mixed lineage leukemia proteins has plant homeodomain (PHD)-mediated E3 ligase activity. J Biol Chem. 2012;287:43410–6. doi: 10.1074/jbc.M112.423855. PubMed DOI PMC

Grow EJ, Wysocka J. Flipping MLL1’s switch one proline at a time. Cell. 2010;141:1108–1010. doi: 10.1016/j.cell.2010.06.013. PubMed DOI

Marschalek R. Systematic classification of Mixed-Lineage Leukemia fusion partners predicts additional cancer pathways. Ann Lab Med. 2016;36:85–100. doi: 10.3343/alm.2016.36.2.85. PubMed DOI PMC