t(9;11)(p21;q23) KMT2A/MLLT3
2016-03-01 Jeroen Knijnenburg , Jeroen Knijnenburg Affiliation1.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands. [email protected]
2.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Abstract
Review on t(9;11)(p21;q23), with data on clinics, and the genes involved.
Clinics and Pathology
Disease
Acute myeloid leukemia (AML).
Phenotype stem cell origin
Most often found in acute monocytic and myelomonocytic leukaemias, although occasionally also seen in AML with or without maturation (WHO 2008).
M5 most often (especially M5a, M4); both found in de novo and therapy related AML with antitopoisomerase II drugs (epipodophyllotoxins, anthracyclins, actinomycin D).
Immunophenotype typically shows positivity for CD11, CD13, CD15 and CD33, but less often shows positivity for CD14, CD34 and lymphoid markers.
M5 most often (especially M5a, M4); both found in de novo and therapy related AML with antitopoisomerase II drugs (epipodophyllotoxins, anthracyclins, actinomycin D).
Immunophenotype typically shows positivity for CD11, CD13, CD15 and CD33, but less often shows positivity for CD14, CD34 and lymphoid markers.
Epidemiology
May occur at any age, but is more common in children, being present in 5-12% of paediatric and 1-2% of adult AML, and equally common in males and females.
Clinics
Organomegaly, frequent central nervous system (CNS) involvement, especially in de novo cases; no preceding myelodysplastic phase, unlike classic therapy related AML with chromosome 5 and/or 7 involvement, short interval from initial drug therapy (may even be of 1-2 yrs). Patients may present with disseminated intravascular coagulation and may have tissue infiltration.
Cytology
Absence of trilineage dysplasia, unlike classic therapy related AML.
Prognosis
Survival is described as poor to intermediate, being superior to AML with other KMT2A translocations.
Cytogenetics
Cytogenetics morphological
May easily be overlooked. Previously described as t(9;11)(p22;q23) based on band estimation, but nowadays it is known that MLLT3 is located in 9p21.3 based on molecular positioning.
Cytogenetics molecular
FISH or RT-PCR is indicated in cases with poor chromosome morphology or in cases where the translocation is expected in cases based on morphology, immunophenotype or clinical presentation.
Additional anomalies
Variants
Complex 3 way translocations t(9;11;Var) involving a (variable) third chromosome and insertions have been described, and showed that der(11) is the crucial on
Genes Involved and Proteins
Gene name
MLLT3 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3)
Location
9p21.3
Protein description
Contains a nuclear targeting sequence; transcriptional activator; nuclear localisation.
Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Protein description
Contains two DNA binding motifs (a AT hook, and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation.
Result of the Chromosomal Anomaly
Description
5 KMT2A- 3 MLLT3; variable breakpoints.N-term -- AT hook and DNA methyltransferase from KMT2A (1444 amino acids) fused to the 192 C-term amino acids from MLLT3 (as breakpoints are variable, this is only an exemple); 180 kDa.
Expression localisation
Nuclear localisation.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 34830251 | 2021 | Modeling, Synthesis, and Biological Evaluation of Potential Retinoid-X-Receptor (RXR) Selective Agonists: Analogs of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahyro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) and 6-(Ethyl(4-isobutoxy-3-isopropylphenyl)amino)nicotinic Acid (NEt-4IB). | 86 |
| 36555852 | 2022 | An Isochroman Analog of CD3254 and Allyl-, Isochroman-Analogs of NEt-TMN Prove to Be More Potent Retinoid-X-Receptor (RXR) Selective Agonists Than Bexarotene. | 82 |
| 39329074 | 2024 | Activating mutations remodel the chromatin accessibility landscape to drive distinct regulatory networks in KMT2A-rearranged acute leukemia. | 75 |
| 39834944 | 2024 | Loss of SMAD1 in acute myeloid leukemia with KMT2A::AFF1 and KMT2A::MLLT3 fusion genes. | 72 |
| 37019972 | 2023 | Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication. | 71 |
| 36843114 | 2023 | Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes. | 70 |
| 29720585 | 2018 | De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia. | 70 |
| 33375773 | 2022 | Epigenetic changes in human model KMT2A leukemias highlight early events during leukemogenesis. | 69 |
| 39380002 | 2024 | The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency. | 68 |
| 33419897 | 2021 | Therapy-induced Deletion in 11q23 Leading to Fusion of KMT2A With ARHGEF12 and Development of B Lineage Acute Lymphoplastic Leukemia in a Child Treated for Acute Myeloid Leukemia Caused by t(9;11)(p21;q23)/KMT2A-MLLT3. | 66 |
| 35793392 | 2022 | In vivo genome-wide CRISPR screening in murine acute myeloid leukemia uncovers microenvironmental dependencies. | 65 |
| 32414848 | 2021 | Combinatorial efficacy of entospletinib and chemotherapy in patient-derived xenograft models of infant acute lymphoblastic leukemia. | 60 |
| 35153769 | 2021 | Novel Compounds Synergize With Venetoclax to Target KMT2A-Rearranged Pediatric Acute Myeloid Leukemia. | 60 |
| 39093953 | 2024 | The E3 ubiquitin ligase Herc1 modulates the response to nucleoside analogs in acute myeloid leukemia. | 58 |
| 33803739 | 2021 | Induction of AML Preleukemic Fusion Genes in HSPCs and DNA Damage Response in Preleukemic Fusion Gene Positive Samples. | 58 |
| 35884834 | 2022 | Molecular Measurable Residual Disease Assessment before Hematopoietic Stem Cell Transplantation in Pediatric Acute Myeloid Leukemia Patients: A Retrospective Study by the I-BFM Study Group. | 51 |
| 33020282 | 2020 | Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/KMT2A. | 50 |
| 37113989 | 2023 | Whole transcriptome sequencing reveals HOXD11-AGAP3, a novel fusion transcript in the Indian acute leukemia cohort. | 46 |
| 36585787 | 2023 | Discovery of fusion circular RNAs in leukemia with KMT2A::AFF1 rearrangements by the new software CircFusion. | 45 |
| 39858509 | 2025 | Lipopolymers as the Basis of Non-Viral Delivery of Therapeutic siRNA Nanoparticles in a Leukemia (MOLM-13) Model. | 44 |
| 35326705 | 2022 | CDK6 Degradation Is Counteracted by p16(INK4A) and p18(INK4C) in AML. | 42 |
| 38965370 | 2024 | Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study. | 40 |
| 38226414 | 2024 | Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia. | 39 |
| 36452349 | 2022 | Analytical study of RUNX1-RUNXT1, PML-RARA, CBFB-MYH11, BCR-ABL1(p210) , and KMT2-MLLT3 in Mexican children with acute myeloid leukemia: A multicenter study of the Mexican interinstitutional group for the identification of the causes of childhood leukemia (MIGICCL). | 39 |
| 26648836 | 2015 | Cytogenetic and Molecular Findings in Children with Acute Lymphoblastic Leukemia: Experience of a Single Institution in Argentina. | 38 |
| 38427924 | 2024 | Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC). | 37 |
| 38621200 | 2024 | Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia. | 35 |
| 35677155 | 2022 | The Combination of Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Delays KMT2A-Rearranged Leukemia Progression. | 35 |
| 34134472 | 2022 | RXRA DT448/9PP generates a dominant active variant capable of inducing maturation in acute myeloid leukemia cells. | 32 |
| 31807181 | 2019 | An extra chromosome 9 derived from either a normal chromosome 9 or a derivative chromosome 9 in a patient with acute myeloid leukemia positive for t(9;11)(p21.3;q23.3): A case report. | 30 |
| 35918824 | 2022 | Fusion transcript analysis reveals slower response kinetics than multiparameter flow cytometry in childhood acute myeloid leukaemia. | 27 |
| 34330316 | 2021 | Mature B cell acute lymphoblastic leukaemia with KMT2A-MLLT3 transcripts in children: three case reports and literature reviews. | 26 |
| 38143534 | 2023 | A single scalp nodule as the first presentation of acute lymphoblastic leukemia (KMT2A::MLLT3) in a healthy-appearing infant: a case report. | 21 |
| 33469688 | 2021 | Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival. | 20 |
| 35933338 | 2022 | Poor treatment responses were related to poor outcomes in pediatric B cell acute lymphoblastic leukemia with KMT2A rearrangements. | 19 |
| 33303709 | 2020 | Changing the frequency and spectra of chromosomal aberrations in Korean patients with acute leukemia in a tertiary care hospital. | 19 |
| 34120595 | 2021 | Novel combined variants of WT1 and TET2 in a refractory and recurrent AML patient. | 16 |
| 30953031 | 2019 | FLT3(N676K) drives acute myeloid leukemia in a xenograft model of KMT2A-MLLT3 leukemogenesis. | 15 |
| 35467057 | 2022 | PAX5 alterations in an infant case of KMT2A-rearranged leukemia with lineage switch. | 15 |
| 38162585 | 2024 | Acute myeloid leukemia cutis with KMT2A::MLLT3 fusion presenting with leonine facies. | 10 |
| 31745420 | 2019 | KMT2A-MLLT3 AML Masquerading as JMML may Disguise Fatal Leukemia. | 8 |
| 36930260 | 2023 | Sustained spontaneous remission in KMT2A-MLLT3 mutated myeloid sarcoma. | 0 |
| 36653696 | 2023 | Comprehensive molecular understanding of pediatric acute myeloid leukemia. | 0 |
| 35506873 | 2022 | Apparent coexistence of ETV6::RUNX1 and KMT2A::MLLT3 fusions due to a nonproductive KMT2A rearrangement in B-ALL. | 0 |
| 33871895 | 2021 | A case of KMT2A-MLLT3 fusion-positive mature B-cell acute lymphoblastic leukemia. | 0 |
| 36472792 | 2023 | Lineage switch in a pediatric patient with KMT2A-MLLT3 from acute megakaryoblastic leukemia to T cell acute lymphoblastic leukemia at the fourth relapse after allo-HSCT: with literature review. | 0 |
| 39626355 | 2025 | TIFAB modulates metabolic pathways in KMT2A::MLLT3-induced AML through HNF4A. | 0 |
| 39633068 | 2025 | HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia. | 0 |
| 36358022 | 2023 | The adverse impact of ecotropic viral integration site-1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes. | 0 |
| 28595195 | 2017 | GAS6 Oncogene and Reverse MLLT3-KMT2A Duplications in an Infant with Acute Myeloid Leukemia and a Novel Complex Hyperdiploid Karyotype: Detailed High-Resolution Molecular Cytogenetic Studies. | 0 |
| 33827367 | 2021 | Is acute lymphoblastic leukemia with mature B-cell phenotype and KMT2A rearrangements a new entity? A systematic review and meta-analysis. | 0 |
| 31701557 | 2019 | Establishment and characterization of a DOT1L inhibitor-sensitive human acute monocytic leukemia cell line YBT-5 with a novel KMT2A-MLLT3 fusion. | 0 |
| 34894139 | 2022 | Detection of a Cryptic KMT2A/AFDN Gene Fusion [ins(6;11)(q27;q23q23)] in a Pediatric Patient with Newly Diagnosed Acute Myeloid Leukemia. | 0 |
| 30277115 | 2019 | Panoramic view of common fusion genes in a large cohort of Chinese de novo acute myeloid leukemia patients. | 0 |
| 32992102 | 2020 | First report of t(5;11) KMT2A-MAML1 fusion in de novo infant acute lymphoblastic leukemia. | 0 |
| 31205223 | 2019 | Primary Cutaneous Diffuse Large B-Cell Lymphoma With KMT2A-MLLT3: An Infantile Case Study. | 0 |
| 28871137 | 2018 | C-terminal BRE overexpression in 11q23-rearranged and t(8;16) acute myeloid leukemia is caused by intragenic transcription initiation. | 0 |
| 33150819 | 2021 | KMT2A-rearranged diffuse large B-cell lymphoma in a child: a case report and molecular characterization. | 0 |
| 39891826 | 2025 | Establishment of a high-risk pediatric AML-derived cell line YCU-AML2 with genetic and metabolic vulnerabilities. | 0 |
| 32368831 | 2020 | Impact of immunophenotypic characteristics on genetic subgrouping in childhood acute lymphoblastic leukemia: Tokyo Children's Cancer Study Group (TCCSG) study L04-16. | 0 |
| 29532520 | 2018 | Clinicopathological characteristics of de novo and secondary myeloid sarcoma: A monocentric retrospective study. | 0 |
| 33392975 | 2021 | Pediatric blastic plasmacytoid dendritic cell neoplasm: report of four cases and review of literature. | 0 |
| 30203571 | 2018 | KMT2A (MLL) rearrangements observed in pediatric/young adult T-lymphoblastic leukemia/lymphoma: A 10-year review from a single cytogenetic laboratory. | 0 |
| 39704147 | 2024 | Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia. | 0 |
| 39672769 | 2024 | Next-generation sequencing RNA fusion panel for the diagnosis of haematological malignancies. | 0 |
| 32175599 | 2020 | Measurable residual disease assessment by qPCR in peripheral blood is an informative tool for disease surveillance in childhood acute myeloid leukaemia. | 0 |
| 28785923 | 2017 | A Case of Acute Myeloid Leukemia with Novel Translocation t(6;11)(p22.2;q23) and Concurrent Insertion ins(11;9)(q23;p21.3p21.3). | 0 |
| 30701458 | 2019 | Molecular profiling of adult acute myeloid and lymphoid leukemia in a major referral center in Lebanon: a 10-year experience report and review of the literature. | 0 |
Bibliography
No bibliography items were found for this article.
Summary
Fusion gene
KMT2A/MLLT3 KMT2A (11q23.3) MLLT3 (9p21.3) TIC
t(9;11)(p21;q23) KMT2A/MLLT3 G- banding (left) - Courtesy Jean-Luc Lai and Alain Vanderhaegen (top 2 rows), Courtesy Diane H Norback, Eric B Johnson, and Sara Morrison-Delap, UW Cytogenetic Services (rows 3 to 6); Courtesy Adriana Zamecnikova (rows 7 and 8); R-banding (right): top: - Courtesy Pascale Cornillet-Lefebvre and Stu00e9phanie Struski, center top: t(9;11)+der(9)t(9;11) - Courtesy Christiane Charrin; bottom 2: - Courtesy Hossein Mossafa. FISH: u201cRedu201d chromosomes - Courtesy Pascale Cornillet-Lefebvre and Stu00e9phanie Struski. The probe is MLL; one signal is on the normal 11, one signal on the der(11), and one signal (arrow) on the der(9); pale blue chromosomes - Courtesy Hossein Mossafa (AN: abnormal). (); bottom 3: Hybridization with Kreatech KMT2A/MLLT3 t(9;11) fusion probe (Leica Biosystems, US) showing hybridization on normal (A) and on metaphases with t(9;11) (B,C). - Courtesy Adriana Zamecnikova.
Citation
Jeroen Knijnenburg ; Jeroen Knijnenburg
t(9;11)(p21;q23) KMT2A/MLLT3
Atlas Genet Cytogenet Oncol Haematol. 2016-03-01
Online version: http://atlasgeneticsoncology.org/haematological/1001/t(9;11)(p21;q23)-kmt2a-mllt3
Historical Card
1997-12-01 t(9;11)(p21;q23) KMT2A/MLLT3 by Jean-Loup Huret,Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
